BACKGROUND:Schizophrenia (SCH) is a severe neuropsychiatric disorder associated with complex neurobiological alterations and suboptimal therapeutic outcomes. Increasing evidence indicates that mitochondrial dysfunction may contribute to SCH pathophysiology through impaired energy metabolism, oxidative stress, altered calcium homeostasis, and dysregulation of neuronal function. This review aims to summarize current knowledge regarding mitochondrial abnormalities in schizophrenia and to explore their potential involvement in the mechanisms of action of antipsychotic drugs. SUBJECTS AND METHODS:A comprehensive review of the current literature was performed, focusing on human studies, cellular and animal models investigating mitochondrial alterations in schizophrenia, as well as studies evaluating the effects of antipsychotic medications on mitochondrial structure and function. RESULTS:Available evidence demonstrates structural, molecular, and functional mitochondrial abnormalities in schizophrenia, including alterations in mitochondrial density, respiratory chain activity, oxidative phosphorylation, ATP production, and redox regulation. Antipsychotic drugs influence mitochondrial pathways in a complex and drug-specific manner. Some antipsychotics may impair mitochondrial respiration and increase oxidative stress, whereas others may exert compensatory or protective effects. Mitochondrial alterations may also contribute to cognitive impairment, negative symptoms, treatment response variability, and metabolic adverse effects associated with antipsychotic therapy. CONCLUSIONS:Mitochondrial dysfunction represents an important component of schizophrenia pathophysiology and a potential therapeutic target. The interaction between mitochondrial pathways and antipsychotic drug effects highlights mitochondria as a possible pharmacodynamic interface for personalized treatment strategies. Further in vivo studies and biomarker-based approaches are required to clarify drug-mitochondria interactions and improve therapeutic outcomes in schizophrenia.
BACKGROUND:The history of mental science is marked by a divide between the subjective, energetic models of psychoanalysis and the objective models of computational neuroscience. Reductionist approaches often fail to bridge this gap or adequately explain the structural complexity of psychopathology. This conceptual synthesis aims to propose a unified, testable neurocomputational framework anchored in the Free Energy Principle (FEP). SUBJECTS AND METHODS:We conduct a theoretical synthesis mapping classical psychodynamic constructs onto the computational dynamics of Active Inference and neuromodulatory neurobiology. We formalize Freud's "Wish" as a high-precision allostatic prior, and drive as prediction error that compels the system to perform work. The Extended Reticular Thalamic Activating System (ERTAS) is analyzed as the physical operator of this economy. RESULTS:Catharsis (discharge/primary process) is mapped as the efficient minimization of free energy via established habits, mediated by routing dopaminergic drive into the dorsal striatum and stabilized by 5-HT1A signaling. Cathexis (binding/secondary process) involves inhibiting immediate discharge for generative model revision, triggered by the lateral habenula and mediated by 5-HT2A signaling. Consolidation occurs via the Gs pathway. We detail a serotonergic "precision switch" acting as a meta-regulator of the Ego, arbitrating between stability, reactivity, and growth. CONCLUSIONS:The mind-brain functions as a hierarchical generative model striving to minimize entropy. This integrated model reframes psychopathology (e.g., depression, mania, psychosis) as "computational pathologies" of precision weighting where the switch between binding and discharge becomes stuck. This provides a rational basis for precision psychiatry, integrating pharmacological modulation of gain control with psychotherapeutic restructuring.
This study aimed to investigate the experiences of fellow patients following the suicide of a group member. Data were collected via a semi-structured interview conducted in a focus group, which comprised of eight patients attending therapy program in the Day hospital for early intervention. Their patients´ reactions reflected the process of mourning and concern for each other and for their own well-being. They were satisfied with the post-suicide actions of the therapy team, which instilled in them a sense of community and support, and some of them even showed signs of post-traumatic growth. We hope that these experiences may serve as a foundation for the development of more effective therapeutic strategies to lessen the trauma of suicide in group therapy.
OBJECTIVE:This article highlights the potential of repetitive Transcranial Magnetic Stimulation (rTMS) in treating antenatal depression (AD), particularly in pregnant individuals for whom standard treatments are limited due to psychological and pharmacological concerns. AD often goes underrecognized and undertreated, despite serious risks to maternal and fetal health. METHODS:We present a case report of a pregnant patient with chronic, recurrent major depressive disorder (MDD) who received rTMS using an intermittent theta burst stimulation (iTBS) protocol. Treatment was safely administered and well tolerated during pregnancy. Clinical outcomes were assessed using the Hamilton Depression Rating Scale (HAM-D) and the Generalized Anxiety Disorder 7-item scale (GAD-7). RESULTS:The patient showed rapid, sustained improvement in depressive and anxiety symptoms, with no adverse effects. CONCLUSIONS:This case suggests that rTMS, particularly iTBS, may represent a promising and well-tolerated non-pharmacological option for antenatal depression in selected patients. However, conclusions regarding efficacy and safety remain limited by the single-case design and require confirmation in larger controlled studies.
While (Cochrane-oriented) evidence based medicine favours RCTs and RCT-based meta-analyses, psychiatry also highlights the values of individualised medicine, complexity sciences and medical epistemology. In a similar way, meta-theoretical considerations put RCTs into perspective: (i) randomisation does not necessarily generate analogous samples, (ii) differences between normal and actual distributions impact on statistical outcomes, (iii) Likert scales may not produce interval data, which are prerequisite for statistical processing, (iv) medical data may possess dynamic characteristics, and (v) standardised research designs have to be revisited from a correspondence-theoretical point of view. To overcome typical flaws, statistical correction, reliable ways of sample splitting and dynamic simulation models are in the ascendant.
