2026-03-19
Leah Simon, Halford Warlick, Armena Jafarmadar, Ernesto Joubran, Marianne Koleng, Christina Regine Owens-Charles, Priyanka Ramanathan, Jorge Rubinos Rodriguez, Stephanie Singer, Vincent S. Gallicchio
The use of lithium (Li) for borderline personality disorder (BPD) is limited as the result of a lack of robust clinical evidence with few clinical studies reported. Although a few studies provide supportive evidence for Li use in addressing certain symptoms such as anger management, impulsivity, and inducing self-harm. Therapies for BPD are psychosocial in nature and serve as the primary treatment for BPD. Based on prior clinical management of lithium use in mental health disorders, providers should investigate its usage in the treatment of BPD. The topic is the subject of this review.
DOI: 10.3389/fnbeh.2026.17070072026-03-18
Karem Vazquez-Roman, Warren Burggren
Severe tissue hypoxia, resulting from cardiac dysfunction for example, is increasingly recognized as a trigger for neurobehavioral change. However, the impact of tissue hypoxia on anxiety-like behavior and disinhibition during development remains poorly understood. Zebrafish larvae provide an effective vertebrate model to evaluate how hypoxia influences behavior in early life. We assigned larvae to three groups: (1) normoxic control, (2) acute severe hypoxic exposure (HE) using cardiac dysfunction as evidence of exposure severity, or (3) HE plus 12 h exposure to 0.3 μmol AZ3 (p38 MAPK inhibitor). At one- and 2-weeks post-exposure we quantified survival, morphometrics, and behavioral measurements (emergence latency, thigmotaxis, zone occupancy, novel object approach, and velocity). Survival differed significantly among all groups (P < 0.001). Untreated HE reduced occupancy of the novel object zone 21% relative to controls at 2 weeks (P = 0.04), indicating diminished neophilia (attraction to novel objects). p38 MAPK inhibition increased body mass (P < 0.001 vs. controls) and prevented the length restriction seen in HE, but also increased by 17% the time spent in thigmotaxis zone compared to HE larvae alone (P = 0.04), consistent with increased anxiety-like behavior. Neither emergence latency nor velocity differed between groups, but both variables changed in the three groups after 1 week decreasing and increasing respectively. Novelty approach distance was unaffected by treatment. Thus, acute early-life hypoxic exposure in zebrafish—severe enough to induce cardiac injury among other forms of likely tissue damage—results in statistically significant but modest decreases in exploratory behavior. P38 MAPK inhibition stimulates growth compared to controls, and also decreases exploratory behavior compared to hypoxic exposure alone and promotes small anxiety-like responses without altering general locomotion. The results highlight the importance of integrating behavioral endpoints into hypoxia exposure research and suggest that targeting p38 MAPK may carry neurobehavioral trade-offs.
DOI: 10.3389/fnbeh.2026.17178562026-03-12
Lu Han, Xingyu Chen, Xinyu Li, Peiyun Zhang, Jinlan Jiang, Xinxuan Lyu, Yanbing Lu, Yuzhen Chen, Wei Jin, Lihong Li
ObjectiveThis study aimed to investigate the cross-sectional associations of multidimensional psychosocial stress and body mass index (BMI) with depression risk.MethodsIn this cross-sectional study, 222 participants (123 with depression, 99 controls) completed questionnaires assessing depression (BDI-II), six domains of psychosocial stress (family, work, financial, academic, interpersonal, emotional), BMI, and lifestyle factors. Multivariable logistic regression was used to examine independent associations, with exploratory subgroup analyses by age and gender.ResultsMultivariate analysis indicates that, family stress (OR = 3.47, 95% CI: 1.96–6.15), academic stress (OR = 1.96, 95% CI: 1.14–3.38), and interpersonal stress (OR = 2.34, 95% CI: 1.36–4.03) were independently associated with higher odds of depression. Higher BMI was associated with lower odds of depression (OR = 0.90, 95% CI: 0.85–0.96); however, this inverse association may be confounded by unmeasured factors such as antidepressant use and should be interpreted cautiously. An extreme association with alcohol abstinence (OR = 0.05) was based on a very small subgroup (n = 14) and requires cautious interpretation. Exploratory subgroup analyses suggested variations in these associations.ConclusionSpecific psychosocial stressors are associated with depression risk in this sample. The counterintuitive finding regarding BMI warrants investigation in studies controlling for medication use. The subgroup findings are preliminary and require replication in larger cohorts.
DOI: 10.3389/fnbeh.2026.17869602026-03-10
Stella Panou, Lucia Lucy Privitera
Multiple sclerosis (MS) is a chronic autoimmune demyelinating disorder that affects the brain and spinal cord. MS is characterized by different neurological and cognitive impairments. Several lines of evidence suggest sex-based differences in the incidence, clinical course and pathophysiology of the disease. Epidemiological data show that women are three times more likely to suffer from MS compared to men and tend to present symptoms earlier. Other evidence indicates that men experience more aggressive forms of MS and women respond better to certain disease-modifying drugs. In this mini review, we summarized recent findings on biological, hormonal and psychological factors underpinning these differences, with reproductive stage being recognized as a key variable to be considered in drug safety and efficacy. Beyond biology, sex and gender influence perception of the disease, quality of life and management. Recognizing sex and gender as important factors in MS supports the move toward precision medicine, leading to care that is not only more effective but also more equitable.
DOI: 10.3389/fnbeh.2026.17773612026-03-10
Logan Mills, Henry Zou, Akram Alnounou, Morgan Smeltzer, Tessa Kravchenko, Theotonius Gomes
BackgroundWernicke’s encephalopathy (WE) is an acute neurologic emergency resulting from thiamine deficiency that can cause irreversible injury if treatment is delayed. Although often associated with alcohol use, WE also occurs in the setting of malnutrition, dysphagia, chronic illness, and malignancy. Dysphagia-related WE is rare and typically linked to impaired oral intake. We report a case of a 26-year-old woman with 3 months of dysphagia and subsequent poor oral intake who developed WE.Case reportA 26-year-old woman with type 2 diabetes and hypothyroidism presented for confusion, speech incoherence, and gait instability following 3 months of dysphagia. She was hemodynamically stable, and her thyroid, autoimmune, toxic, and infectious workups were negative. Although repeated computed tomography was negative, magnetic resonance imaging showed signal changes in the mammillary bodies, posterior midbrain, and medial thalami, indicating Wernicke’s encephalopathy. Her thiamine, folate, and B12 levels were replaced, and her mentation and coordination improved. A swallow study showed no physiologic dysphagia. She was discharged on oral thiamine supplementation and referred to psychiatry for the presumed psychogenic etiology of her dysphagia, given the distressing life events prior to hospitalization.SignificanceThe classic WE triad of confusion, oculomotor abnormalities, and ataxia presents in a minority of patients; hence, atypical presentations may be overlooked. Our patient demonstrated how WE can be induced by nutritional deficiencies secondary to functional or psychogenic dysphagia. Furthermore, this case highlights the importance of prompt clinical intervention via thiamine repletion despite inconclusive initial imaging, as delayed treatment can result in permanent complications.
DOI: 10.3389/fnbeh.2026.17807752026-02-24
Axel Allache, Marc Auriacombe, Jean-Marc Alexandre, Fuschia Serre
The addiction term is sometimes overused, both in the media and popular discourse, to describe excessive engagement in everyday behaviors such as sugar consumption, screen use, or physical exercise. This overuse may reflect the fact that rewarding behaviors, much like the use of rewarding substances, can lead to repeated use, occasionally beyond what is considered reasonable and with significant negative consequences. This raises fundamental questions: by which criteria can an addiction be identified? Is the phenomenon the same for substances and behaviors? This perspective article proposes to explore these questions by examining the relevance of craving, defined as an intense, persistent, but involuntary desire to use a specific substance/behavior. Although craving is well-established as a core criterion for substance addictions, with strong prognostic value, clinical utility, it has not yet been formally integrated into diagnostic classifications for behavioral addictions. This perspective article reviews recent evidence supporting that craving may represent a transdiagnostic construct across substance and behavioral addictions.
DOI: 10.3389/fnbeh.2026.17708952026-02-24
Begum Saral, Durmus Atilgan, Deniz Adiay, Nazlican Filazi, Hakan Ozturk, Gorkem Kismali, Goncalo Da Graca Pereira, Aykut Ozkul, Yasemin Salgirli Demirbas
IntroductionAging in dogs is a multifactorial process involving behavioral, cognitive, immunological, and microbiota-related changes, yet distinguishing healthy from pathological aging remains challenging. This exploratory study aimed to evaluate physiological indicators of health by integrating pain evaluation and cognitive testing in senior companion dogs.MethodsEighteen companion dogs aged ≥8 years underwent standardized behavioral and cognitive evaluations (Mini C-BARQ, DISHAA, object choice test), chronic pain assessment (Helsinki Chronic Pain Index), and quality-of-life (QoL) scoring. Hematological parameters, serum brain-derived neurotrophic factor (BDNF), and Th1/Th2 ratios were measured as physiological indicators, while fecal samples were analyzed via 16S rRNA sequencing for microbiota profiling.ResultsAll dogs scored above the chronic pain threshold (mean HCPI: 28.72), although caregiver-reported QoL ratings suggested good overall wellbeing. Cognitive testing yielded low average scores on the DISHAA (mean: 9.05), with only one dog showing mild cognitive decline; however, mean performance on the object choice test was low (1.94/5). Mean serum BDNF concentration was 0.154 ng/dL (SD: 0.082) and correlated positively with red blood cell (RBC) count and negatively with MCV, MCH, and MCHC (p ≤ 0.05). Immune profiling patterns suggested Th2 polarization. The gut microbiota was dominated by Firmicutes and Bacteroidetes. Principal Component Analysis (PCA) identified two primary dimensions of biological variation: a pain–immune–microbiota axis, defined by higher chronic pain scores, Th2 polarization, increased Prevotella abundance, and higher DISHAA scores, and a second component reflecting microbiota compositional variation.DiscussionThese preliminary findings highlight potential interactions between pain, microbiota composition, and immune dysregulation, suggesting their possible utility as candidate indicators for differentiating healthy from pathological aging in dogs.
DOI: 10.3389/fnbeh.2026.16898072026-02-24
Lindsay L. Sailer, Amit Hanadari-Levy, Alexander G. Ophir
Adolescence is a sensitive period for the maturation of neural circuits governing goal-directed social behaviors and stress regulation. Disruption of stable social relationships during adolescence can alter neuropeptide and dopaminergic systems that shape adult social behaviors. We investigated the behavioral and neurobiological consequences of adolescent social instability stress (SIS) in male prairie voles (Microtus ochrogaster), a species that forms selective social bonds between peers, mating partners, and parents and their offspring. During adolescence, SIS subjects experienced repeated reshuffling of cage mates to disrupt stable peer bonds, while control (CTL) subjects remained in fixed pairs. Home cage observations after and right before each reshuffling revealed that SIS subjects exhibited reduced affiliative contact and sustained social investigation compared to CTL subjects, despite no group differences in body weight throughout adolescence. Moreover, SIS and CTL groups did not differ in social zone duration or latency to approach a novel conspecific during the social approach test (SAT). Stress phenotypes were classified by assessing the duration of social zone occupancy during the SAT under baseline and stimulus-present conditions. Remarkably, all SIS subjects expressed a consistent stress resilient phenotype in contrast to CTL subjects whose responses were more variable, spanning both stress resilient and susceptible phenotypes. Gene receptor expression analyses revealed no group differences in oxytocin (Oxtr), arginine vasopressin (Avpr1a), and dopamine (Drd1 and Drd2) gene expression within the lateral septum (LS), nucleus accumbens (NAc), or anterior cingulate cortex (ACC), brain regions important for modulating goal-directed social behaviors and stress responses. However, correlation analyses indicated distinct relationships between gene receptor expression and social behaviors across groups, including a negative association between LS- Avpr1a expression and the latency to approach a novel conspecific in only CTL subjects. Additionally, associations between ACC-Drd2 expression and the latency to approach a stimulus were in opposing directions between groups. Correlation analyses solely between gene receptor expression revealed the loss of oxytocin-dopamine receptor coupling in the LS and ACC of SIS but not CTL subjects. Together, these findings suggest that adolescent SIS does not globally suppress social behavior but instead may reorganize social reward circuitry to promote behavioral flexibility and stress resilience.
DOI: 10.3389/fnbeh.2026.17615492026-02-23
Jaclyn Iannucci, Lavanya Venkatasamy, Michael Davis, Thao-April Nguyen, Ghazal Suhani Yadav, Victoria Nugeness, Reagan Dominy, Gabriel Maisonnave Arisi, M. Karen Newell-Rogers, Lee A. Shapiro
IntroductionTraumatic brain injury (TBI) is a major cause of death and disability worldwide. Alterations to adult hippocampal neurogenesis have been identified following experimental TBI, and there are known sex differences in the response to TBI. However, few studies have investigated sex differences in neurogenesis following TBI. One of the common signatures of TBI is an inflammatory response. This includes activation of antigen presenting cells, including B lymphocytes. Previous studies have identified a pathogenic role for a B cell subset, CLIP+ B cells, following TBI. However, the role of CLIP antagonism on the adult hippocampal neurogenic niche has not been fully elucidated following a TBI, and sex differences have not been previously explored. This is extremely important because sex differences in adult neurogenesis have been previously identified. Thus, the current study was designed to test the hypothesis that CLIP antagonism after TBI would differentially influence adult neurogenesis and associated behavioral outcomes in male and female subjects.Methods10-week-old male and female C57bl/6J mice received either lateral fluid percussion injury (FPI) or sham surgery, followed 30 min later by the administration of a CLIP antagonist peptide (CAP) or vehicle. At 35 days post-FPI, all mice underwent neurobehavioral testing using the pattern recognition test (PRT). After behavioral testing, at 60 post-FPI, harvested brains were analyzed for DCX+ newborn neurons and GFAP+ astrocytes in the hippocampus to assess the effects on the neurogenic niche.ResultsFPI induced deficits in the PRT that were more pronounced in females and improved by CLIP antagonism. Immunohistological assessments revealed that female mice had reduced DCX+ neurons in the dentate gyrus and increased hippocampal GFAP+ astrocytes at 60 days post-FPI, regardless of injury or treatment condition. Further analysis showed that FPI in male mice leads to increased hypertrophy of GFAP+ radial glial in the dentate gyrus and increased presentation of hilar basal dendrites. These changes were not observed in female mice.ConclusionThe results from this study demonstrate sex differences in the neurogenic niche and associated cognitive impairment following FPI and suggest a role for CLIP after FPI in mediating these sex differences.
DOI: 10.3389/fnbeh.2026.1768730