Abstract
Previous reviews have focused on neurobiological and physiological mechanisms underlying conversion disorder, but they do not usually distinguish between negative and positive conversion symptoms. Some authors have proposed that different phenomena should underlie both situations and that diverse emotion regulation strategies (under- vs. overregulation of affect) should be related to different internal experiences (excitatory experiences with hyperarousal manifestations vs. inhibitory experiences coexisting with hypoarousal states, respectively). After a careful review of the literature, we conclude that there is not a unique theory comprising all findings. Nevertheless, we have also collected some replicated findings that should be salient. Patients manifesting positive conversion symptoms tended to present with limbic hyperfunction, not sufficiently counteracted by prefrontal control. This leads to underregulation of affect mechanisms, increased emotional reactivity and autonomic hyperarousal. The opposite pattern (with a prefrontal overfunction working as a cognitive brake over the limbic system) has been described during negative conversion manifestations. We also highlight the influence of fronto-limbic circuits over cortico-striato-thalamo-cortical circuits’ regulation, whose horizontal and vertical synchronization has been at the spotlight of the genesis of conversion and dissociative disorders.
Introduction
Many studies and reviews have focused on neurobiological and physiological mechanisms underlying conversion disorder, but they do not usually distinguish between negative conversion symptoms (translating sensorimotor pseudodeficits such as hysterical paralysis, aphonia, blindness, deafness and sensory loss) and positive conversion symptoms (excessive activity manifested by aberrant movements, psychogenic tremor, pseudoseizures, gait disturbances, etc.). Some authors have proposed that positive conversion symptoms appear to be linked to underregulation of affect and cognitive preoccupation-coertion responses (Van Dijke et al., 2010; Kozlowska et al., 2011). In this case, the prefrontal cortex (PFC) is not able to stop the limbic emotional avalanche. This situation is also accompanied by a hyperarousal state characterized by sympathetic dominance (Van Dijke et al., 2010). On the other hand, negative conversion has been linked to cognitive inhibitory mechanisms and emotional overregulation, associating affective numbness and hypoarousal (Van der Hart et al., 2006; Lanius et al., 2014a). In this situation, prefrontal areas such as the orbitofrontal cortex (OFC) and the ventromedial prefrontal cortex (vmPFC) would be overactive and somehow would function as a limbic brake (corticolimbic disconnection model, by Sierra and Berrios, 1988) (Sierra et al., 2002).
These two types of responses exceed the emotional window of tolerance by excess or defect (Gross, 1999; Ogden and Minton, 2000). In this sense, Porges’ polyvagal theory has overcome the classical sympathetic-parasympathetic opposition model by emphasizing the role of the vagal system as the most important emotion regulator (Porges, 2007, 2009). He proposed a hierarchical model in which when the context is understood as being safe, the social communication system operates through the ventral vagus (the highest hierarchical subsystem). When external demand becomes more intense, attention must be externally directed and an increase in danger expectation and alertness takes place. It leads to a vagal brake retirement bringing out sympathetic responses (fight or flight). In case of imminent danger coexisting with an inability to escape, immobilization behaviors appear (complete submission or apparent death) as a result of the inhibition of higher systems and the outcrop of the primitive dorsomedial vagus. This model provides a plausible explanation for a frequently observed feature in dissociative and conversion disorders: the arousal instability, characterized by a cyclization between hyperarousal and hypoarousal states (Fisher, 2014).
We can definitely say that there are two main emotion regulation strategies characterized either by an excess or by a defect in the regulation capacities (over- and underregulation of affect, respectively), but a third strategy, characterized by an alternation between the previous strategies, must be considered. It supposes a secondary aim of this review to clarify if these two mechanisms and their concomitant vegetative correlates are related to different neurobiological patterns and diverse clinical manifestations (negative vs. positive symptomatology).
This review article aims to approach current knowledge regarding the neurobiology and physiology of the different types of conversion symptoms. The parallelism of the findings with the appearance of different emotion regulation strategies is also addressed. In the following section, a general point view of the neurobiology of conversion disorder is exposed. Then, specific findings for each clinical subtype (positive vs. negative symptoms) are reviewed, and finally conclusions and discussion are presented.
Neurobiological bases of conversion disorder
In general, a global bilateral increase of frontal and parietal flow has been found in conversion patients, as well as an augmentation of other regions’ activity: the right amygdala, the anterior cingulate cortex (ACC) and the insula (Vuilleumier et al., 2001; Lanius et al., 2014a). The last three structures are essential for emotional stimuli processing and action motivation. Another group of studies alluded to a possible selective decrease of basal ganglia and contralateral thalamus activity which was also linked to the duration of symptoms (Vuilleumier et al., 2001; Atmaca et al., 2006). Conversion disorders translate the malfunctioning of neural circuits linking volition, movement and perception (Yaźići and Kostakoglu, 1998). Cortico-striato-thalamo-cortical circuits’ suppression would take place under the influence of diverse emotional or motivational states. Vuilleumier postulates that the basal ganglia, in general, and the caudate nucleus, in particular, would be particularly well placed in order to modulate motor processes based on emotional states (processed in the limbic system) (Black et al., 2004). It has also been hypothesized that the variety of neurofunctional changes described could be pointing at a dysrhythmia syndrome or thalamo-cortical desynchronization (Llinás et al., 1999). According to some authors, stress causes increases in frontal and limbic activity and leads to cortico-striato-thalamo-cortical removal and sensorimotor conscious processing inhibition (Vuilleumier et al., 2001; Harvey et al., 2006). Similar assumptions had previously been postulated for healthy people with dissociation traits and dissociative patients (Veltman et al., 2005; Elzinga et al., 2007).
Therefore, far from finding a single change in brain function defining conversion disorders, we must consider the existence of high-order representation alterations in the areas where sensorimotor function should be integrated with meanings, relevance, motivation or action (Vuilleumier, 2005). Additionally, the question of a hemispheric lateralization of conversion symptoms remains opened. Traditionally, it was considered that these manifestations were more frequent on the left side of the body, appearing under the influence of the right hemisphere. A parallelism between the classical ‘belle indifference’ and right parietal anosognosia has been proposed (Galin, 1977; Merskey and Watson, 1979; Devinsky et al., 2001). However, the systematic review Stone conducted found a higher frequency of sensory and motor conversion symptoms on the right side of the body questioning the classic conception (Stone et al., 2002).
On the other hand, neurophysiology contributed by verifying the functional integrity of sensory circuits (Vuilleumier, 2005). A decrease in late event-related potentials (p300) during conversion and dissociative episodes has been found, and its reduction disappeared after recovery (Rief et al., 1998; Kimble et al., 2010). The opposite phenomenon has been objectified in individuals presenting high interoceptive awareness (Pollatos et al., 2005). The attenuation of the p300 wave has been interpreted as representing negative feedback from the temporary medial lobe up to the cortex in order to diminish input information, attentional resources and the update of working memory. That way, long- and short-term emotional memory hyperfunction could be avoided (Kirino, 2006). Some authors have associated alterations in memory functions and decreased hippocampal volume with increased glucocorticoid exposure and proinflammatory states. Both situations are related to high and sustained stress levels (Blackwood et al., 1987; Shea et al., 2005; Kirino, 2006), which could be the link between trauma exposure and emotional memory impairments.
From the vegetative point of view, a diminished habituation has been described in different clinical conversion manifestations, while other neurotic disorders have been presented with a habituation delay (Lader and Sartorius, 1968; Moldofsky and England, 1975; Horvath et al., 1980; Hetzel-Riggin and Wilber, 2010). Conversion patients also tended to interpret repeated stimuli as if they were new (Horvath et al., 1980). It is unclear whether these findings are related to increased threat detection, to a higher arousal baseline, to neurophysiological activation impairments or to decision-making and memory integration alterations.
Conversion clinical subtypes: neurobiological and physiological features
We will separately attend neurobiological and physiological features for each conversion clinical subtype, since the existing literature does not support the uniformity of conversion responses.
Motor loss: paralysis and paresis
Different neurobiological mechanisms underlying conversion paralysis have been postulated. Ludwig (Ludwig, 1972) proposes a selective corticofugal inhibition of afferent stimuli which could be caused by the inhibition of sensorimotor areas mediated by the limbic system. However, this hypothesis has been superseded by new event-related potentials studies (Harvey et al., 2006), and nowadays the existence of a motor intention loss secondary to affective states is the most plausible explanation in opposition to former theories considering a decrease in early cortical sensory processing (Mailis-Gagnon et al., 2003; Vuilleumier, 2005). Event-related potentials studies have generally found a decrease in the p300 wave when conversion patients were asked to move the paralyzed limb, which has not been observed in healthy volunteers simulating the same symptoms nor in patients during the action preparation (Lorenz et al., 1998). It was postulated that the execution should be interrupted (Marshall et al., 1997; Blakemore et al., 2013). Other hypotheses include the possibility of a self-monitory deficit underlying this symptom, as well as a limbic processing or high-order regulation impairment (Roelofs et al., 2003; Vuilleumier, 2005; Cojan et al., 2009; Voon et al., 2010; Mehta et al., 2013).
Several authors have suggested that basal and thalamic areas would control emotional movement modulation and that its deafferentation would be the key in the integration impairments underlying these kinds of disorders (Vuilleumier et al., 2001; Lanius et al., 2014a). Previous studies have found alterations in other regions such as the frontal cortex and the lower OFC (Vuilleumier, 2005). Studies based on various paradigms suggest that there may be a disconnection between the dorsolateral prefrontal cortex (dlPFC) and motor areas (Marshall et al., 1997; Spence et al., 2000; De Lange et al., 2010). The OFC and ACC have been identified as responsible for the inhibitory effects of the dlPFC over the motor cortex (Marshall et al., 1997; Halligan et al., 2000; Amoruso, 2010). The dlPFC would play a role on motor planning alterations appearing in conversion disorders. However, when globally assessed, the PFC would show an activation during the attempt to move the paralyzed limb in chronic conversion patients (Marshall et al., 1997), with a marked activity increase at medial and superior temporal regions (De Lange et al., 2007). Hypofunction at some areas such as the inferior parietal cortex, cerebellum, contralateral primary sensorimotor cortex and premotor cortex have also been observed (Marshall et al., 1997; Spence et al., 2000; Black et al., 2004; De Lange et al., 2007; Stone et al., 2007; Van Beilen et al., 2011). These findings suggest the existence of a prefrontal inhibition of planning and movement execution circuits. In this sense, Saj proposed two different mechanisms leading to conversion paralysis: the first one consisted of an explicit inhibition and was linked to vmPFC and parietal (precuneus) integrity (Cojan et al., 2009), while the second one was based on an implicit inhibition and was modulated by limbic areas such as the insula, amygdala and ACC (Saj et al., 2009, 2014).
Vegetative parameters have also been investigated. Hovarth found a decrease in skin conductance habituation in conversion patients (with negative symptoms) compared to anxious ones (Horvath et al., 1980). An excessive activation of vmPFC, OFC and ACC would lead to a decrease in sympathetic tone with regard to previous models linking up these structures (Nagai et al., 2004).
To sum up, there is no unitary hypothesis concerning the neurobiology of conversion paralysis. Nevertheless, prefrontal hyperactivation permits a top-down regulation similar to the one described during overregulation of affect strategies. The existence of bottom-up attentional processes is also a possible explanation and it could complete the previous hypothesis.
Conversion immobility
First of all, we aim to review the role of ethology and evolutionary biology in describing different behavioral responses that mammals activate in the case of threat detection. Lang et al. (2000) studied the defensive reflexes in animals and humans and proposed a defensive waterfall model involving four stages. The first stage (‘pre-encounter stage’) is previous to the onset of any defensive mechanisms, and at that moment, appetitive and motivational functions take place. In the second stage (‘encounter stage’) (with potential proximity of the predator), the animal passes through a freezing state, directs the attention and focuses towards the potential threat increasing the reactivity and facilitating future flight responses. During attentional freezing, a decrease in heart rate and a change in somatic reflexes are found (startle reflex potentiation) (Lang et al., 2000; Elbert and Schauer, 2010; Bovin et al., 2014; Corrigan, 2014). In the third stage (‘post-encounter stage’), the animal changes the defensive posture in order to respond with a fight or flight mechanism appearing with an increase in heart rate, skin reactivity and startle reflex. If flight or coping is impossible, a tonic immobilization will take place (immobilization with fear, also called freezing of the fight/flight response), where physical restraint is accompanied by high activation, stiffness and analgesia via opioid release. Frontal lobe disinhibition takes place mediated by limbic hyperactivation (projecting through the periacuedutal gray matter and activating a group of interneurons placed on the reticular formation), which finally inhibits motor spinal neurons (Klemm, 1976, 1989; Fanselow, 1991; Moskowitz, 2004; Bovin et al., 2014). After an extensive review, Bovin et al. (2014) appreciate that tonic immobility could coexist with an excess of both sympathetic and parasympathetic tone.
This last model is interesting but does not include other important responses. In this sense, Shauer and Elbert proposed in 2010 an extended model of defensive cascade including six types of responses occurring after the pre-meeting state: freeze, fight, flight, tonic immobility, fading/dizziness and fainting. The authors argued that the first half of the responses would be primarily mediated by the sympathetic, while the second half would translate parasympathetic activation (Elbert and Schauer, 2010). Therefore, atonic immobility and fainting are modulated by a parasympathetic dorsovagal dominance (Bandler et al., 2000) and a ventrolateral periacueductal gray matter (vlPAGM) activation. According to the polyvagal theory, a failure on both social communication and fight-flight subsystems would take place, and it would allow the primitive vagus to emerge (Porges, 2007, 2009, 2011). Lanius postulated that this phenomenon was associated to an autoanalgesic state (mediated by endogenous opiods) (Lanius et al., 2014).
Sensory loss
The affected limb stimulation paradigm has been broadly used when studying sensory conversive anesthesia, but controversial results have been described. Nevertheless, one of the most replicated findings is the decrease in sensory cortex activation (Tiihonen et al., 1995; Mailis-Gagnon et al., 2003; Ghaffar et al., 2006). Deactivations have also been described in the posterior parietal cortex and frontal cortex, keeping rostral ACC normally activated (Mailis-Gagnon et al., 2003). Hyperactivation has been found in diverse areas such as the insula, ACC, OFC, caudate nucleus and right temporo-parietal junction, bilateral dlPFC, ventroanterior thalamic nuclei and left angular gyrus (Burke et al., 2014). The frontal cortex in general and some specific areas such as the OFC and dlPFC have been found hyperactive, in a similar pattern as it was previously described for conversion paralysis (Tiihonen et al., 1995). This suggests that an impairment in volition and emotion regulation circuitry exists, leading to a somatosensory cortex inhibition through top-down mechanisms. Cortico-striato-thalamo-cortical circuits modulate this phenomenon through motivational factors. Hereby, we postulate that sensory cortex inhibition at later stages (secondary to an excessive frontal control) could play a role by counteracting the previous sensory overactivation at a baseline level (Lader and Sartorius, 1968; Moldofsky and England, 1975; Hoechstetter et al., 2002). This mechanism is congruent with an overregulation of affect strategy.
Meanwhile, similar activation patterns have been described during conversion blindness. Primary visual area inhibition mediated by limbic and frontal activation has been hypothesized (Werring et al., 2004).
We have not found any neurofunctional studies involving patients suffering from conversion deafness or aphonia during the acute episode. In our opinion, hysterical deafness could have a common underlying mechanism with other negative conversion symptoms. Functional/conversive dysphonia and aphonia are heterogeneous clinical constructs (Butcher, 1995; Maniecka-Aleksandrowicz et al., 2006), and we would probably find diverse neurofunctional alterations underlying these different clinical manifestations. Further investigation is needed in order to give light to the neurobiology responsible for this kind of symptoms.
Positive motor conversion symptoms: tremor, aberrant postures, abnormal movements, speech and gait functional impairments
Voon found smaller activation in the supplementary motor area (involved in action initiation) in patients with positive motor conversion, as well as greater activation in the right amygdala, the left anterior insula and bilateral posterior cingulated cortex whose function is related to emotional relevance. Furthermore, a subgroup of patients suffering from conversion tremor presented less connectivity between the supplementary motor area and the bilateral dlPFC (Voon et al., 2011). A decreased activation in parietal areas has been found as well as poorer connectivity between parietal cortex, limbic areas and sensorimotor cortex (Hallett, 2010).
Voon proposed for this type of conversion symptoms a theory according to which conversion motor representations previously mapped could trigger, in an alertness context, the voluntary action selection system which would be hypoactive and functionally disconnected from regulatory prefrontal top-down mechanisms (Voon et al., 2011). In this sense, a failure on high-order prefrontal regulation of motor control has been postulated. Movement self-authorship would also be altered, and previous cognitive schemes would lead to psychogenic movement onset (Pareés et al., 2012; Kranick et al., 2013).
Motor prediction and motor expectation impairments would arise as a result of the hypoactivity of the temporo-parietal junction. It involves the construction of typical conversive motor representations which could be subsequently automatically triggered in case of threat detection. Voon’s research group found for this conversion subtype an opposite connection pattern between the dlPFC and motor areas compared to the one described for conversion paralysis, as well as greater connectivity between the amygdala and the supplementary motor area. This hyperconnectivity has also been observed in patients when passively viewing pictures of happy and fear faces vs. neutral faces. The authors concluded that a hyperarousal state used to dominate in these patients, consorting with Seignourel’s findings (Seignourel et al., 2007; Voon et al., 2010). As we postulate, it would be linked to the emotion regulation pattern called underregulation of affect.
Pseudoseizures
Pseudoseizures are considered positive motor conversion manifestations with particular characteristics and clinical heterogeneity (Guz et al., 2003; Auxéméry et al., 2011; Patidar et al., 2013). Because of this, several authors encourage us to separate them from other motor functional symptoms.
A decrease in the right motor and premotor cortex as well as in the cerebellum thickness has been found in patients with pseudoepileptic seizures (Labate et al., 2012). Van der Kruijs described a greater connectivity between emotion-related areas (insula), executive control areas (inferior frontal gyrus and parietal cortex) and movement control regions (precentral sulcus) in these patients. This pattern of connectivity was also linked to dissociation scores (Van der Kruijs et al., 2012). Despite having found an excessive connectivity between these areas, neurophysiological and functional neuroimaging studies diffusion tensor imaging (DTI) evidenced that a generalized desynchronization and uncoupling exists (Duncan, 2011; Barzegaran et al., 2012; Ding et al., 2013), and that it is more plausible in prefrontal and parietal areas (Van der Kruijs et al., 2012). These studies bring us back to a possible cortico-strio-thalamo-cortical dysrhythmia as Llinás et al. (1999) propounded. Desynchronization of information integration circuits leads to an emotion regulation and executive control failure where PFC and other related areas are unable to stop the underlying limbic avalanche (Lanius et al., 2014b). In this context, high emotional reactivity arises, consistent with well-known clinical features and personality manifestations in conversion patients suffering from pseudoseizures (Galimberti et al., 2003; Almis et al., 2013).
Regarding concomitant vegetative findings in these patients, a decrease in the heart rate variability, both at baseline and after recovery, has been described. This could be related to a decreased parasympathetic activity (Bakvis et al., 2009; Ponnusamy et al., 2011).
Discussion and conclusions
According to the current investigation into the neurobiological and physiological patterns that underlie different conversion manifestations, we can conclude that there is no unique theory joining all the findings. We are too far to being able to integrate neurophysiology, neuroimaging and clinical approaches in a unitary theory. We would like to accentuate the importance of models such as Lanius et al.’s (2014a) or the polyvalgal perspective proposed by Porges (2007, 2009, 2011) because of the inclusive nature of both proposals. We highlight their ability taking into account the diversity of clinical, emotional and vegetative manifestations that appear in these patients.
On the other hand, positive and negative clinical manifestations do frequently coexist in the same subject. It is also unlikely to find durable, emotion and clinical independent physiological states. In this context, it is common to find in these patients a cyclation between hyper- and hypoarousal states that could be understood as a result of arousal instability and/or cyclization between different parts (theory of structural dissociation of the personality) (Van der Hart et al., 2006). The exact moment, the internal and external demands, as well as the clinical manifestations modulate the final neurobiological and physiological correlate that should be understood as dynamic (time and state dependent).
Although we are aware of the variability of the findings described above, we have also collected some replicated findings that should be salient (Table 1). Patients manifesting positive conversion symptoms tended to present a limbic hyperfunction not sufficiently counteracted by prefrontal control systems. This leads to underregulation of affect mechanisms, increased emotional reactivity and autonomic hyperarousal (by vagal brake cessation and sympathetic predominance associated with fight/flight responses). The opposite pattern (with a PFC overfunction working as a cognitive brake over the limbic system) has been described during negative conversion manifestations. This neurofunctional and cognitive top-down regulation would have its emotional counterpart in emotional overregulation of affect. This mechanism is linked to affect blunting affect and inhibitory experiences. The individual operates under primitive vagal activation (parasympathetic predominance leading to hypoarousal). Likewise, we would like to highlight the influence that fronto-limbic circuits have on cortico-striato-thalamo-cortical circuits’ regulation, whose horizontal and vertical synchronization has been at the spotlight of the genesis of conversion and dissociative disorders (Lanius et al., 2014b).
Main findings linking the different clinical conversion manifestations with their associated neurobiological and physiological patterns, as well as emotion regulation predominant strategies.
| Conversion symptoms | Clinical subtypes | Neurobiological pattern | Physiological predominant pattern | Emotion regulation predominant strategy |
|---|---|---|---|---|
| Motor loss | Paralysis and paresis | Global frontal hyperfunction with reduced connectivity between dlPFC and premotor areas. Increased activation in OFC and ACC. | Hipoarousal at baseline, associating decreased habituation. Low basal sympathetic tone. | Overregulation of affect |
| Immobility/freezing | Attentional freezing/aware immobility | Increased dopaminergic transmission at mesolimbic circuits and at the bed nucleus of the stria terminalis. | Sympathetic activation. Hyperarousal state. | Overregulation of affect |
| Fight or flight freezing | Increased cannabinoid and noradrenergic transmission Alteration of ACC and HPA axis. | Sympathetic activation. Hyperarousal state. | Underregulation of affect | |
| Tonic immobility/immobility with fear | Amygdala hyperactivation causing frontal lobe disinhibition and projecting to the PAGM (it activates the reticular ascendant system and inhibits spinal cord motor neurons). | Simultaneous parasympathetic and sympathetic activation Hypo/hyperarousal; Arousal instability. | Cycling between under- and overregulation strategies | |
| Fainting and atonic immobility | Endogenous opioids release (autoanalgesia) that activates vlPAGM and its connections to the medulla and the OFC. | Dorsovagal parasympathetic activation. Hypoarousal. | Overregulation of affect | |
| Sensorial loss | Anesthesia, deafness, blindness and aphony | OFC and dlPFC hyperfunction, as well as other frontal and limbic areas show similar hyperactivity. Sensory cortical areas deafferentation. | Initial hyperreactivity, activating top-down inhibitory responses later on. Hypoarousal. | Overregulation of affect |
| Positive motor conversion | Tremor, gait disturbances and abnormal movements | Increased amygdala-supplementary motor area connectivity. | Sympathetic activation. Hyperarousal state. | Underregulation of affect |
| Pseudoseizures | Pseudoepileptic seizures | Hyperconnectivity between the insula, inferior frontal cortex, parietal cortex and precental sulcus. Desynchronization and decoupling between cortical areas. | Decreased parasympathetic tone. Sympathetic activation. Hyperarousal. | Underregulation of affect |
It would be interesting for future investigations to work on integration theories instead of enumerating discrete findings. The role of different hormones, neuropeptides and other neurotransmitters should also be integrated with previous neurofunctional and neurophysiological research.
We finally note the incongruence between self-reported and objectified physiological parameters in these patients. Subjective assessment and self-report of emotional and physiological states are not a reliable guide in order to discover real biological features. In this sense, electrophysiological and/or neurofunctional assessment becomes determinant. They can help us to settle down whether the observed clinical findings and internal self-reported experiences are consistent with bodily experiences, cognitive processes and physiological underlying states.
About the authors
Lucía del Río-Casanova is an MD and psychiatrist vinculated to the University Hospital of Santiago de Compostela (Spain). She is also a PhD student and the subject of the PhD thesis is emotion regulation in conversion disorders.
Anabel González Vázquez is a psychiatrist vinculated to the University Hospital of A Coruña (Spain), where she leads the ‘Trauma and dissociation program’. She received her PhD in Psychiatry from the University of Santiago de Compostela. She is the author of two books dealing with dissociative disorders and borderline personality disorders.
Mario Páramo Fernández is a psychiatrist, PhD and the head of the Department of Psychiatry at the University Hospital of Santiago de Compostela (Spain). He is also a professor of psychiatry at the University of Santiago de Compostela. He has a broad research experience in the psychiatry field. He has been involved in various clinical trials and has also collaborated in different publications concerning the genetics and epidemiology of psychiatric disorders. He has been the president of the regional Psychiatric Association and has participated in several clinical practice guidelines.
Julio Brenlla is a psychiatrist, PhD and head of the Department of Psychiatry of the Gil Casares Hospital (Santiago de Compostela, Spain). He is also a professor of psychiatry at the University of Santiago de Compostela. He has broad research experience in the psychiatry field, and has been involved in various epidemiological and clinical studies. He has directed several PhD theses.
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