Biological Psychiatry最新文献

Postpartum psychosis (PP) is an acute and severe psychiatric illness with onset within weeks after delivery and a high risk of suicide and infanticide. Most women with PP experience severe mood symptoms, including mania, mixed episodes, or depression with psychotic features. Impaired cognition, irritability, and agitation are also common. The specific timing of PP strongly suggests a biological basis, because the postpartum time period is characterized by profound endocrine, immune, neuroanatomical, and physiological changes in the brain. Genetic studies show a unique risk architecture, partly shared with bipolar disorder. PP stands out as one of the most distinct clinical phenotypes in psychiatry due to its characteristic rapid onset, severity, phenomenology, treatment response, and prognosis. Despite this, as of August 2025, PP does not have a distinct diagnostic classification in the DSM. This expert consensus panel, in close collaboration with patient organizations and key interested partners, recommends classifying PP as a distinct category within DSM-5 and ICD-11. We recommend classification within the bipolar disorders chapter of the DSM because 1) most women with PP have prominent affective symptoms; 2) treatment response to lithium and electroconvulsive therapy is excellent; 3) in half of the cases, first-onset PP is also the first onset of bipolar disorder; 4) pregnant women with bipolar disorder are at very high risk of PP; and 5) the genetic risk architecture for PP is distinct but overlapping with bipolar disorder. This consensus statement summarizes scientific evidence that PP is a distinct mental illness within the bipolar spectrum; correct classification will improve detection and treatment.

Background: The impact of acute cannabis exposure on brain function and cognitive performance varies among individuals. Acute effects of cannabis on behavior may be absent or benign in chronic users, while occasional users experience significant impairment in day-to-day operations. It is hypothesized that repeated cannabis use induces neuroadaptations leading to tolerance and desensitization, although the precise mechanisms underlying these adaptations remain unclear.

Methods: In this study, we investigated acute and persistent effects of vaporized cannabis on brain dynamics in a placebo-controlled neuroimaging trial involving occasional (n = 23) and chronic (n = 20) cannabis users. Functional resting-state data were collected to assess dynamic functional connectivity changes during intoxication and their association with attentional performance and normative cannabinoid CB₁ receptor density.

Results: Cannabis intoxication induced significant acute alterations in the dynamics of brain network organization, as shown by a reduced occurrence of a hyperconnected brain state in both user groups. Chronic users also displayed decreased segregation of brain networks independent of treatment condition, suggesting persisting neuroadaptations. Dynamic reconfiguration of hyperconnected brain motifs correlated with attentional performance, which was most impaired in occasional users, indicating tolerance in chronic users. Both the acute and persistent effects of cannabis on dynamic brain state organization were significantly associated with spatial CB₁ receptor density.

Conclusions: Acute cannabis-induced cognitive impairment is influenced by (persistent) network reconfigurations and CB₁ receptor density. These findings emphasize the relevance of neural dynamics and individual neuroadaptations to (prolonged) cannabis use when assessing the behavioral effects of cannabis in therapeutic, legal, and societal settings.

Background: Schizophrenia remains a leading cause of disability globally. Elevated striatal dopamine synthesis capacity is a hallmark of its pathophysiology, but it is unknown whether this can be reduced and whether such reductions lead to symptom improvement. Trace amine-associated receptor 1 (TAAR1) may regulate dopaminergic function, and ulotaront (SEP-363856), a TAAR1 agonist, offers a potential novel treatment strategy.

Methods: We conducted combined translational preclinical and clinical test of mechanism studies. Preclinical work involved TAAR1 knockout (KO) and wild-type mice (n = 27), as well as ex vivo striatal brain slices. In a phase I open-label trial, 22 patients with symptomatic schizophrenia (mean age = 32.5 years; 72.7% male) received 14 days of adjunctive ulotaront treatment. Dopamine synthesis capacity (K_i) was measured using [18F]-DOPA PET in animals and humans. Dopamine release in brain slices was assessed using fast-scan cyclic voltammetry.

Results: TAAR1-KO mice showed significantly higher striatal K_i than wild-type controls (p < 0.05). Ulotaront reduced evoked dopamine release in brain slices after single (p < 0.0005) and repeated (p < 0.005) stimulation. In patients, ulotaront significantly reduced striatal K_i (p < 0.01), particularly in the putamen. Reductions in K_i correlated with improvements in positive symptoms (r = 0.5, p < 0.05), but not with changes in negative or total symptoms. The most common adverse events were somnolence and dizziness.

Conclusions: TAAR1 regulates dopamine synthesis and release. Adjunctive ulotaront reduces presynaptic dopamine function and psychotic symptoms in schizophrenia. These findings support TAAR1 as a promising target for treating antipsychotic non-responsive schizophrenia and other dopaminergic disorders.

Background: Dyslexia is a common learning disorder characterized by difficulty processing written language despite normal intelligence and adequate educational resources. KIAA0319 is one of nine genes reproducibly associated with reading performance, but the molecular basis of its function remains unclear.

Methods: To investigate the role of KIAA0319 in neurodevelopment, we used CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 to generate KIAA0319 knockout (KIAA0319^-/-) human embryonic stem cells, which were then differentiated into human cortical organoids (hCOs). We assessed developmental and transcriptomic changes using morphological analysis, immunostaining, EdU assays, calcium imaging, and single-cell RNA sequencing (scRNA-seq).

Results: KIAA0319^-/- hCOs were smaller, displayed morphological abnormalities, and showed disrupted neurogenesis and impaired neuronal maturation. scRNA-seq showed that KIAA0319^-/- neural progenitor cells favored a truncated radial glia fate over neuronal maturation. Transcriptomic analysis showed coordinated dysregulation across multiple dyslexia-associated genes, implicating KIAA0319 in a broader regulatory network involved in primary cilia formation, cortical organization, and neural network connectivity.

Conclusions: These findings suggest that dyslexia-associated genes, including KIAA0319, may regulate core neurodevelopmental processes beyond reading and language, pointing to a broader biological framework for understanding the etiology of dyslexia.

Background: There are large knowledge gaps in the etiology of attention-deficit/hyperactivity disorder (ADHD), and although it is a prevalent and highly heritable neurodevelopmental disorder, diagnosis can be challenging. We aimed to assess the association of circulating blood plasma microRNAs (miRNAs) at birth with ADHD for use as biomarker candidates and build an miRNA-based prediction model.

Methods: Our study population consisted of 206 children with ADHD (33.0% female), 207 control children (33.8% female), and their parents from the MoBa (Norwegian Mother, Father, and Child Cohort Study). Expression levels of 51 selected miRNAs in plasma from children's cord blood at birth and from both parents during early pregnancy were quantified by quantitative polymerase chain reaction and tested for association with children's ADHD diagnosis and ADHD symptom scores based on ratings by parents.

Results: Seven miRNAs were differentially expressed at birth in children with ADHD and control children (false discovery rate < .05), and 31 had a statistically significant linear relationship with parent-rated ADHD symptom score at 8 years. A 19-miRNA ADHD prediction model achieved good discrimination in the test population (area under the receiver operating curve = 0.959, accuracy = 0.893). Functional analysis for the 19-miRNA prediction set revealed involvement in several highly relevant pathways, e.g., dopaminergic synapse, circadian rhythm, and axon guidance. We also found that parental miRNA expression levels significantly associated with children's ADHD diagnoses and/or ADHD symptoms scores.

Conclusions: We showed that expression levels of circulating miRNAs at birth may be used to predict increased risk of ADHD diagnosis, and our 19-miRNA set should be included in future efforts to develop a biomarker panel.