Compulsive sexual behavior disorder (CSBD) is a newly classified clinical condition characterized by persistent difficulty in controlling sexual impulses, repetitive sexual activity despite adverse consequences, and significant distress or impairment in various life areas. This narrative review explores the clinical and neurobiological overlaps between CSBD and selected mental disorders, including mood and anxiety disorders, attention-deficit/hyperactivity disorder, autism spectrum disorder, obsessive-compulsive disorder, and specific personality disorders. The review emphasizes shared mechanisms, such as dysregulation of the dopaminergic reward system, impairments in emotional regulation, and altered connectivity in brain regions responsible for impulse control and affect processing. Structural and functional neural changes associated with impulsivity, such as abnormalities in the prefrontal cortex, orbitofrontal cortex, and limbic system, are discussed as potential contributors to both CSBD and its comorbid conditions. These findings support a dimensional approach to diagnosis and treatment, highlighting the need for integrated clinical strategies that account for overlapping symptoms and underlying vulnerabilities. This narrative review explores the clinical and neurobiological overlaps between CSBD and selected mental disorders, including mood and anxiety disorders, attention-deficit/hyperactivity disorder, autism spectrum disorder, obsessive-compulsive disorder, and specific personality disorders. The review emphasizes shared mechanisms, such as dysregulation of the dopaminergic reward system, impairments in emotional regulation, and altered connectivity in brain regions responsible for impulse control and affect processing. Structural and functional neural changes associated with impulsivity, such as abnormalities in the prefrontal cortex, orbitofrontal cortex, and limbic system, are discussed as potential contributors to both CSBD and its comorbid conditions. These findings support a dimensional approach to diagnosis and treatment, highlighting the need for integrated clinical strategies that account for overlapping symptoms and underlying vulnerabilities. Chronic activation of the HPA axis due to prolonged stress leads to adaptive changes in serotonergic and dopaminergic systems, which may increase impulsivity and reduce the ability to control impulsive behaviors, including sexual ones [ 6 ]. Moreover, despite the frequently observed decrease in libido among depressed individuals, there are reports that a significant proportion of people with depression (15-25%) paradoxically experience increased sexual arousal [ 5 ]. The underlying mechanism of this sexual paradox is the aforementioned compensatory mechanism. Furthermore, sexual behaviors often serve as a tool for short-term emotional regulation in individuals with depression. Engaging in sexual activities can be perceived as a strategy to avoid negative emotions, additionally triggering a temporary feeling of relief associated with dopamine release in the reward system, reinforcing such behavior. Repeating sexual behaviors for self-regulation strengthens impulsive patterns while perpetuating an avoidance schema for negative emotions, instead of effectively processing them, deepens the interaction between these disorders [ 5 ]. Analyzing the mechanisms of co-occurrence of ADHD and CSBD, particular attention was drawn to dysfunctions of the dopaminergic reward system. reported that 24% of individuals with high-functioning ASD engage in paraphilic sexual fantasies, including pedophilia, voyeurism, or sadomasochism [ 30 ]. When analyzing the pathogenesis of ASD in the context of comorbidity with CSBD, special attention has been given to dysfunctions within the dopaminergic reward system. Similarities in the dysfunctions of the dopaminergic system in ASD and CSBD have been mainly observed within the mesocorticolimbic pathway, which is responsible for regulating emotions, impulsivity, motivation, and reward processing. In the context of sexual behaviors, structural similarities between ASD and CSBD may result in similar behavioral disturbances and explain their comorbidity. In conclusion, the primary mechanism contributing to the comorbidity of ASD and CSBD appears to be the dysfunction within the dopaminergic reward system, leading to behavioral disturbances and altered responses to sexual stimuli. Despite numerous studies confirming differences in the sexuality of individuals with ASD, the underlying mechanisms remain not fully understood. Obsessive-compulsive disorder Studies indicate that 5-7% of individuals with OCD may develop CSBD during their lifetime, with 75% of cases involving men [ 32 ]. From the perspective of emotional self-regulation, CSBD may emerge as a consequence of affective or anxiety disorders; conversely, its progression could exacerbate neural dysregulation, increasing vulnerability to depression. In affective disorders, CSBD might function as a primary disorder, a secondary phenomenon, or a compensatory response. Similarly, serotonergic and dopaminergic dysregulation in the prefrontal cortex, particularly in the orbitofrontal cortex (OFC), is central to obsessive-compulsive disorder (OCD), where CSBD symptoms may present as obsessions or compulsions. The OFC’s involvement in erotic stimulus regulation and the striatum’s role in reward processing imply that disrupted connectivity between these structures in CSBD contributes to maladaptive sexual motivation. These disruptions may also extend to affective and anxiety symptoms, reflecting broader behavioral dysregulation. Ultimately, alterations in OFC-striatum-limbic connectivity may stem from CSBD or represent a predispositional factor for multiple disorders, underscoring the potential for shared neurobiological predictors rather than direct causality. Despite being a newly classified diagnosis, CSBD's clinical relevance is increasingly acknowledged.

Obsessive-compulsive disorder (OCD) has long been conceptualized as a neuron-centric disorder of cortico-striato-thalamo-cortical (CSTC) circuit dysregulation. However, a growing body of evidence is now reframing this narrative, placing astrocytes-once relegated to passive support roles-at the center of OCD pathophysiology. Astrocytes are critical regulators of glutamate and GABA homeostasis, calcium signaling, and synaptic plasticity, all of which are disrupted in OCD. Recent high-resolution molecular and proteomic studies reveal that specific astrocyte subpopulations, including Crym-positive astrocytes, directly shape excitatory/inhibitory balance and control perseverative behaviors by modulating presynaptic inputs from the orbitofrontal cortex. Disruptions in astrocytic neurotransmitter clearance and dopamine metabolism amplify CSTC circuit hyperactivity and reinforce compulsions. This review reframes OCD as a disorder of neuro-glial dysfunctions, proposing that targeting astrocytic signaling, metabolism, and structural plasticity may unlock transformative therapeutic strategies. By integrating human and animal data, we advocate for a glial-centric model of OCD that not only enhances mechanistic understanding but also opens new frontiers for precision treatment. Astrocytes crucially regulate neurotransmitter homeostasis, synaptic plasticity, and neural circuit function within the cortico‐striato‐thalamo‐cortical network, disruptions of which characterize OCD. By outlining specific astrocytic dysfunctions—such as impaired glutamate and dopamine regulation—the review emphasizes their role in OCD pathology and proposes astrocytes as novel therapeutic targets. This glial‐centric perspective not only broadens mechanistic insights into OCD but also paves the way toward innovative treatments for this complex and debilitating psychiatric disorder. The indirect pathway, functioning as a brake, has an inhibitory effect on the thalamus through indirect projections from the striatum to the GPi via the external GP (GPe; Pauls et al. 2014 ). In healthy individuals, the excitatory direct pathway is modulated by the inhibitory function of the indirect pathway. In OCD patients, an imbalance between these two pathways, with a predominance of the direct pathway, is thought to underlie the manifestations of the disorder (Pauls et al. 2014 ). 1.3. Neurochemical Dysregulation in OCD: The Role of Serotonin, Dopamine, and Glutamate Dysfunctions in serotonergic (5‐HTergic), dopaminergic (DAergic), and glutamatergic (Gluergic) systems have been strongly implicated in OCD (Fawcett et al. 2020 ). 1.3.1. Serotonergic Dysfunction in OCD Selective serotonin reuptake inhibitors (SSRIs) are the first‐line pharmacological treatment for OCD, leading to early hypotheses suggesting that 5‐HTergic deficits play a primary role in the disorder's pathophysiology (Pauls et al. 2014 ). However, direct evidence supporting a primary serotonin abnormality in OCD remains inconclusive. Moreover, the therapeutic limitations of SSRIs highlight the complexity of OCD neurobiology. While these medications provide symptom relief for many patients, 30%–40% of individuals exhibit treatment resistance, indicating that other neurotransmitter systems, such as glutamate and dopamine, also play critical roles in OCD pathology (Fineberg et al. 2012 , 2013 ; Stein et al. 2019 ). The partial efficacy of SSRIs further suggests that 5‐HTergic dysfunction may contribute to, but not fully account for, the compulsive and obsessive features of the disorder. 5‐HTergic receptors play a multifaceted Given the breadth of evidence implicating both neuronal and astrocytic glutamatergic dysfunctions, future research should aim to further elucidate the precise mechanisms by which glutamate homeostasis is disrupted in OCD and explore targeted interventions that restore normal glutamate dynamics in affected circuits. 1.4. Astrocytes: The Missing Link in OCD Pathophysiology? For decades, OCD research has predominantly focused on neuronal dysfunctions within CSTC circuits, emphasizing alterations in neurotransmitter systems such as serotonin, dopamine, and glutamate. The coordinated action of these transporters ensures that synaptic inhibition remains spatially confined, preventing the spillover of GABA between neighboring inhibitory synapses while maintaining long‐range inhibitory modulation. Given the crucial role of excitatory‐inhibitory (E/I) balance in neural network function, disruptions in astrocytic GABA regulation have been implicated in neuropsychiatric disorders, including OCD (Figure 1F ). Beyond GABA uptake, astrocytes also actively release GABA, further influencing inhibitory neurotransmission. Studies using astrocyte‐specific VMAT2 conditional knockout (aVMAT2cKO) mice show that the selective deletion of VMAT2 in medial PFC astrocytes reduces extracellular dopamine levels, alters synaptic plasticity, and impairs cognitive flexibility—deficits closely resembling neurobehavioral alterations seen in OCD (Figure 1B ; Petrelli et al. 2020 ). Notably, restoring VMAT2 expression in astrocytes or L‐DOPA treatment rescues these deficits, highlighting a direct link between astrocytic dopamine dysfunction and OCD‐like behaviors (Petrelli et al. 2023 ). Beyond dopamine depletion, astrocytic dysfunction also leads to maladaptive synaptic plasticity. 2023 ). Beyond dopamine uptake and metabolism, astrocytes actively modulate DAergic receptor signaling, further influencing neural excitability and behavioral regulation. Astrocytes express dopamine D1 and D2 receptors, which regulate intracellular Ca 2+ signaling and gliotransmission (Scofield and Kalivas 2014 ), thereby shaping synaptic plasticity in response to dopamine input. The role of these receptors in astrocytic function is particularly relevant in the context of OCD, as alterations in D1/D2 receptor balance have been implicated in the development of compulsive behaviors (Scofield and Kalivas 2014 ).

(CBGTC loop) is a system of neural circuits in the brain. The loop involves connections between the cortex, the basal ganglia, the thalamus, and back to the The cortico-basal ganglia-thalamo-cortical loop (CBGTC loop) is a system of neural circuits in the brain. The loop involves connections between the cortex, the basal ganglia, the thalamus, and back to the cortex. It is of particular relevance to hyperkinetic and hypokinetic movement disorders, such as Parkinson's disease and Huntington's disease, as well as to mental disorders of control, such as The cortico-basal ganglia-thalamo-cortical loop (CBGTC loop) is a system of neural circuits in the brain. The loop involves connections between the cortex, the basal ganglia, the thalamus, and back to the cortex. It is of particular relevance to hyperkinetic and hypokinetic movement disorders, such as Parkinson's disease and Huntington's disease, as well as to mental disorders of control, such as attention deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder (OCD), and Tourette syndrome. The CBGTC loop primarily consists of modulatory dopaminergic projections from the pars compacta of the substantia nigra, and ventral tegmental area as well as excitatory glutamatergic projections from the cortex to the striatum, where these projections form synapses with excitatory and inhibitory pathways that relay back to the cortex. The loop was originally proposed as a part of a model of the basal ganglia called the parallel processing model, which has been criticized and modified into another model called the center surround model. Current organization schemes characterize cortico-basal ganglia interactions as segregated parallel processing, meaning there is little convergence of distinct cortical areas in the basal ganglia. This is thought to explain the topographically organized functionality of the striatum. The striatum is organized on a rostro-caudal axis, with the rostral putamen and caudate serving associa The cortico-basal ganglia-thalamo-cortical loop (CBGTC loop) is a system of neural circuits in the brain. The loop involves connections between the cortex, the basal ganglia, the thalamus, and back to the cortex. It is of particular relevance to hyperkinetic and hypokinetic movement disorders, such as Parkinson's disease and Huntington's disease, as well as to mental disorders of control, such as attention deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder (OCD), and Tourette syndrome. The CBGTC loop primarily consists of modulatory dopaminergic projections from the pars compacta of the substantia nigra, and ventral tegmental area as well as excitatory glutamatergic projections from the cortex to the striatum, where these projections form synapses with excitatory and inhibitory pathways that relay back to the cortex. The loop was originally proposed as a part of a model of the basal ganglia called the parallel processing model, which has been criticized and modified into another model called the center surround model. Current organization schemes characterize cortico-basal ganglia interactions as segregated parallel processing, meaning there is little convergence of distinct cortical areas in the basal ganglia. This is thought to explain the topographically organized functionality of the striatum. The striatum is organized on a rostro-caudal axis, with the rostral putamen and caudate serving associative and cognitive functions and the caudal areas serving sensorimotor function. Sometimes when the striatum is the expressed target the loop is referred to as the cortico-striatal-thalamic-cortical loop. The two major input structures of the circuit are the striatum and the subthalamic nucleus (STN). The striatum receives inputs from both the cortex and the pars compacta of the substantia nigra (SNc), while the STN only receives cortical inputs. Two pathways emerge from the striatum. One pathway is called the indirect (or NoGo) pathway and is inhibitory. This projects to and inhibits the globus pallidus externus (GPe), resulting in the disinhibition of the globus pallidus internus (GPi), leading to inhibition of the thalamus. This pathway also, as a result of inhibiting the GPe, disinhibits the subthalamic nucleus, which results in excitation of the GPi, and therefore inhibition of the thalamus. The second pathway, is called the direct (or Go) pathway and is excitatory. This pathway inhibits the GPi, resulting in the disinhibition of the thalamus. The direct pathway mostly consists of monosynaptic connections driven by dopamine receptor D1, adenosine A1 receptor, and muscarinic acetylcholine receptor M4, while the indirect pathway relies on connections driven by dopamine receptor D2, adenosine A2A receptor, and muscarinic acetylcholine receptor M1. The parallel CBGTC loops have been segregated according to the functions of associated cortical regions. One scheme involves the division into limbic and motor loops, with the motor loops containing indirect and direct pathways, which are in turn interconnected with the limbic loop that projects into the ventral striatum. The loop has also been divided into limbic, associative, oculomotor, and motor circuits to explain the role of dopamine in the basal ganglia on motivational states. A five loop division based on primary cortical targets has been described as follows: A motor circuit originating in the supplementary motor area, motor cortex, and somatosensory cortex, which in turn projects to the putamen, which projects to the ventrolateral GPi and caudolateral SNr, before returning to the cortex via the ventralis lateralis pars oralis and ventralis lateralis pars medialis. An oculomotor circuit originating in the frontal eye fields projecting to the body of the caudate, and returning via the caudal dorsomedial GPi/ventromedial SNr, and then the lateral ventralis anterior pars magnocellularis and medialis dorsalis pars paralarnellaris. A dorsolateral prefrontal