Background: While depression can be associated with multiple comorbidities, the association between depression and liver injury significantly increases the mortality risk. The aim of this study was to evaluate if moderate alcohol intake affects the rate of clinical relapses in patients treated with antidepressants as monotherapy. Methods: We assessed, over a period of 30 months, the clinical records of 254 patients with depressive disorder, of either gender, without additional pathologies, receiving monotherapy treatment with antidepressants. Thirty-three patients with alcohol abuse, alcoholism or significant cognitive impairment were excluded. The medical and psychiatric history, medication and liver enzyme values were collected and analyzed. Results: Out of the 221 patients who met the inclusion criteria, 78 experienced relapses of depression. The rate of relapse did not correlate with the levels of liver enzymes. Alcohol consumption, as objectified based on GGT levels and the AST/ALT ratio, suggested that men had higher alcohol intake compared to women. Patients treated with serotonin-norepinephrine reuptake inhibitors (SNRIs) with elevated AST levels were approximately 9 times more likely to relapse, while the ones with elevated GGT had a 5.34 times higher risk. While GGT levels remained a marker for relapse in men with elevated GGT, ALT and not AST proved to be a better risk indicator for relapses in male patients. Conclusion: The use of SNRIs in depressed male patients with moderate alcohol intake should be carefully considered, as they might be susceptible to higher risks of relapse compared to alternative antidepressant therapies.

The treatment of acute life-threatening events in patients suffering from chronic pathologies is problematic, as physicians need to consider multisystemic drug effects. Regarding Cerebrolysin, a Sonic Hedgehog signaling pathway amplifier and one of the few approved neurotrophic treatments for stroke patients, concerns of excessive Hedgehog pathway activation that could accelerate NAFLD progression to cirrhosis seem valid. We investigated stroke patients treated with Cerebrolysin that presented elevated levels of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT). We also investigated the efficiency of Cerebrolysin in reversing the neurogenesis inhibition within the hippocampus in a mouse model of NAFLD by evaluating behavior and histological outcomes. NeuN, BrdU and Iba1 positive signals in the cortex and hippocampus of the animals were also observed. Clinically, Cerebrolysin improved AST levels in a majority of stroke patients with hepatic damage. The same treatment in an experimental setup was able to reverse anxiety-like behavior in MCD mice, reducing their freezing time from 333.61 ± 21.81 s in MCD animals to 229.17 ± 26.28 in treated ones. The use of Cerebrolysin did not improve short-term memory nor rescued cell multiplication in the hippocampus after MCD food intake. Understanding the neuroprotective and neurotrophic effects that drugs have on NAFLD patients can significantly contribute to a suitable therapeutic approach.

The prevalence of mental disorders is increasing across the European Union, with at least one in four individuals expected to experience a psychiatric condition at some point in their lifetime. Notably, men and women often present with distinct symptomatology. Among neuropsychiatric disorders, attention-deficit/hyperactivity disorder (ADHD) is the most common and functionally impairing condition in childhood, affecting approximately 5% of minors. Its persistence into adulthood is substantial, with prevalence estimates reaching up to 3% in adult populations. ADHD is characterized by dysregulated dopaminergic signaling, which disrupts reward processing and motivation. Additionally, disturbances in circadian rhythms contribute to sleep dysregulation and metabolic dysfunction, further exacerbating symptom severity. While both mechanisms have been well-documented, their interaction remains insufficiently explored, particularly regarding its implications for diagnosis and treatment optimization. Future research should systematically examine the interplay between dopaminergic and noradrenergic dysfunction and circadian disruptions in ADHD, particularly in relation to symptom expression and comorbid conditions. Experimental paradigms assessing reward processing may provide valuable insights into dopamine and norepinephrine system alterations, while chronotherapeutic interventions-such as light therapy, sleep regulation, and behavioral adjustments-hold promise as potential therapeutic strategies. By integrating perspectives from neurobiology, chronobiology, and psychopharmacology, a more refined and individualized approach to ADHD management can be developed. Advancing this understanding may not only enhance ADHD treatment strategies but also yield novel therapeutic avenues for addressing its frequently co-occurring conditions.

A 56-year-old man presented to the emergency department with pain, swelling, and restricted mobility of the left lower limb and shortness of breath on exertion in the previous 3 days. Seven months prior to this presentation, he had been diagnosed with adult-onset Still’s disease based on the Yamuguchi criteria, after excluding the presence of any other disease. The patient had been treated with prednisolone and methotrexate. Subsequent investigations revealed that he developed bilateral deep venous thrombosis and bilateral pulmonary emboli. This case emphasizes that adult-onset Still’s disease can be a rare but life-threatening cause of venous thromboembolism.

Due to brain plasticity, the nervous system is capable of manifesting behavioral variations, adapted to the influences from both external and internal environment. Multiple neurotransmitters are involved in the mediation of pathological processes at the molecular, cellular, regional, and interregional levels participating in cerebral plasticity, their intervention being responsible for various structural, functional, and behavioral disturbances. The current therapeutic strategies in neuroprotection aim at blocking on different levels, the molecular cascades of the pathophysiological mechanisms responsible for neuronal dysfunctions and ultimately for neuronal death. Different agents influencing these neurotransmitters have demonstrated beneficial effects in neurogenesis and neuroprotection, proved in experimental animal models of focal and global ischemic injuries. Serotonin, dopamine, glutamate, N-methyl-D-aspartate, and nitric oxide have been shown to play a significant role in modulating nervous system injuries. The imidazoline system is one of the important systems involved in human brain functioning. Experimental investigations have revealed the cytoprotective effects of imidazoline I2 receptor ligands against neuronal injury induced by hypoxia in experimental animals. The neuroprotective effects were also highlighted for kappa and delta receptors, whose agonists demonstrated the ability to reduce architectural lesions and to recover neuronal functions of animals with experimentally induced brain ischemia.

Attention-Deficit/Hyperactivity Disorder (ADHD) is increasingly recognized as a neurodevelopmental condition involving both dopaminergic dysfunction and circadian misalignment. While these mechanisms have traditionally been studied independently, their combined impact on symptom expression and comorbidity-particularly with mood disorders, substance use disorders, and obesity-remains insufficiently understood. This review aims to integrate current evidence on the interaction between circadian and dopaminergic dysfunction in ADHD and to evaluate the therapeutic potential of chronobiological interventions. We conducted an integrative review of studies across neurobiology, chronobiology, psychopharmacology, and genetics, including evidence from both human and animal models. The review focuses on molecular and clinical findings related to circadian regulation, dopaminergic signaling, and their interaction in ADHD pathophysiology and treatment response. Evidence indicates that dopaminergic dysregulation contributes to impaired reward processing and motivational deficits, while circadian disruption is associated with sleep disturbances, emotional dysregulation, and metabolic dysfunction. These processes appear to interact bidirectionally, potentially amplifying symptom severity and comorbidity. Emerging findings implicate circadian genes-particularly CRY1-in the regulation of both neural and metabolic pathways. Chronotherapeutic interventions, including light therapy, melatonin supplementation, and sleep-focused behavioral strategies, show promise, particularly when aligned with individual circadian profiles. Elucidating the interplay between circadian misalignment and dopaminergic dysfunction may inform more precise, biomarker-guided treatment strategies in ADHD. Stratified care models that incorporate circadian timing and individual variability have the potential to improve outcomes and address the high comorbidity burden. Large-scale, controlled clinical studies are needed to validate these approaches and facilitate their translation into personalized interventions.