There is growing recognition that substance use is associated with the emergence of psychosis.Elements of post-modernity dominate contemporary social contexts and operate as existential background factors that contribute to the emergence of substance-related psychotic phenomena, particularly use of potent and highly rewarding novel psychoactive substances (NPS). About 25% of first-episode psychoses are substance-induced (SIP). DSM-5 SIP diagnosis is based on the assumption that symptoms are transient and disappear after sustained abstinence. This narrowed definition does not consider the issue of persistent SIP. There is a clear need for a new diagnostic framework that provides reliable, unambiguous clinical criteria to differentiate between comorbid conditions (i.e., schizophrenia patients with a substance use disorder) and substance-related psychoses. In the present contribution, we aim to outline a novel and separate clinical entity: substancerelated exogenous psychosis (SREP). Within this diagnostic category, we refer to both transientand persistent psychoses associated with substance use. SREP is conceived as a distinct psychoticdisorder with psychopathological specificities that clearly differentiate it from schizophrenia. We address differences in terms of clinical presentation, epidemiology, etiological models and treatment response. SREP is characterized by altered states of consciousness, persecutory delusions, visual and cenesthetic hallucinations, impulsivity and psychomotor agitation, affectiveand negative symptoms, a pervasive feeling of unreality and intact insight. Delusions are typically secondary to abnormal perception resulting from a characteristic “sensorialization” of the world. Longitudinal studies are warranted to substantiate our hypothesis of a novel diagnostic categoryand support the clinical validity of SREP. This may have important implications in terms of early differential diagnosis and staging (i.e., between comorbid conditions, persistent and transientsubstance-related psychotic states) as well as choice of treatment interventions.
Repetitive transcranial magnetic stimulation (rTMS) has gained growing interest for the treatment of major depression (MDD) and treatment-resistant depression (TRD). Most knowledge on rTMS comes from human studies as preclinical application has been problematic. However, recent optimization of rTMS in animal models has laid the foundations for improved translational studies. Preclinical studies have the potential to help identify optimal stimulation protocols and shed light on new neurobiological-based rationales for rTMS use. To assess existing evidence regarding rTMS effects on depressive-like symptoms in rodent models, we conducted a comprehensive literature search in accordance with PRISMA guidelines (PROSPERO registration number: CRD42019157549). In addition, we conducted a meta-analysis to determine rTMS efficacy, performing subgroup analyses to examine the impact of different experimental models and neuromodulation parameters. Assessment of the depressive-like phenotype was quite homogeneous whilst rTMS parameters among the 23 included studies varied considerably. Most studies used a stress-induced model. Overall, results show a largely beneficial effect of active rTMS compared to sham stimulation, as reflected in the statistically significant recovery of both helplessness (SDM 1.34 [1.02;1.66]) and anhedonic (SDM 1.87 [1.02;2.72]) profiles. Improvement of the depressive-like phenotype was obtained in all included models and independently of rTMS frequency. Nonetheless, these results have limited predictive value for TRD patients as only antidepressant-sensitive models were used. Extending rTMS studies to other MDD models, corresponding to distinct endophenotypes, and to TRD models is therefore crucial to test rTMS efficacy and to develop cost-effective protocols, with the potential of yielding faster clinical responses in MDD and TRD.
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