<![CDATA[New cohort and global data link teen high-potency cannabis use to higher psychosis, bipolar, and suicide risks. Here’s what psychiatrists and mental health clinicians should know in the era of legalization.]]>

Structural Brain Network Alterations in Relation to Treatment and Illness Severity in Bipolar Disorder

Large-scale T1-weighted MRI studies have established grey-matter abnormalities in bipolar disorder (BD), with our group contributing to consensus findings. However, structural connectivity, particularly within emotion- and reward-related circuits, remains poorly understood. Diffusion-weighted MRI (dMRI) enables investigation of white-matter pathways, yet prior work is constrained by small samples, methodological heterogeneity, and unclear medication effects. We conducted the largest dMRI network analysis in BD, relating symptom burden and polypharmacy to tractography-derived connectivity and graph-theoretic metrics.

Case Report: Prism for PTSD in severe traumatic brain injury with psychiatric comorbidities: two cases

BackgroundTraumatic brain injury (TBI) with post-traumatic stress disorder (PTSD) is treatment-resistant, with conventional psychotherapy showing limited efficacy due to neurocognitive impairments.Case SummaryWe report two patients with severe TBI and psychiatric comorbidities treated with Prism neurofeedback.Case 144-year-old female, 35 years post-childhood TBI, with agoraphobia and hyperacusis, achieved 42% PTSD reduction and substantial functional gains (social reintegration, independent driving) sustained through 4-month follow-up.Case 240-year-old male, 3.5 years post-adult TBI with bipolar II disorder and severe PTSD (PCL-5 = 62), achieved 90% PTSD reduction with complete remission sustained at 1-month follow-up, enabling return to work and family system transformation. Both patients developed personalized regulatory strategies and maintained gains without relapse.ConclusionsPrism neurofeedback demonstrates clinically meaningful outcomes in severe TBI-PTSD where traditional psychotherapy shows limited efficacy. The intervention’s circumvention of cognitive processing demands may explain the favorable outcomes. Controlled trials are warranted.

Sex-specific impact of vitamin D and B9 concentrations on neuroticism: a polygenic score-based study

IntroductionNeuroticism is a personality domain with prognostic value for physical and mental health. To properly inform public health policy, it is crucial to uncover the mechanisms underlying high neuroticism. Many internal and external factors that affect brain development and functioning and therefore might contribute to the variability of neuroticism remain understudied. Among them, the impact of vitamin sufficiency is of great interest, as it is a modifiable factor. This study aimed to evaluate the associations of neuroticism with vitamin D (VD) and vitamin B9 (VB9) using polygenic scores (PGS) in a nonclinical cohort.MethodsWe analyzed data from 348 healthy unrelated individuals, including neuroticism scores on the Eysenck Personality Inventory, VD-PGS, VB9-PGS and PGS for neuroticism-related traits.ResultsThe analysis controlling for demographic and genetic confounders revealed a negative association between VB9-PGS and neuroticism scores in women and a positive association between VD-PGS and neuroticism scores in men. The highest values of the VD-PGS were observed in men, who scored high on both neuroticism and extraversion. In men, unlike women, neuroticism scores were not correlated with PGS for neuroticism but were associated with PGS for bipolar disorder type 1 and alcohol use disorders.ConclusionThe results suggest that the effects on neuroticism of genetic propensity for suboptimal vitamin D and B9 concentrations might differ across the two sexes. The findings are consistent with the idea of the importance of vitamin B9 for emotional stability in women and indicate the involvement of genetic factors predisposing to higher vitamin D levels in excitability-related components of neuroticism in men.
<![CDATA[New evidence shows lithium adds minimal weight in bipolar disorder and explains why some gain occurs—plus practical tips to prevent it.]]>

Self images: an empirical enquiry into Rembrandt’s self-portraits

Many have speculated that events of personal and financial loss in the life of Rembrandt van Rijn (Rembrandt) caused depression and that this is revealed by examination of his work particularly self-portraits painted in old age. Some report detecting various physiological diseases associated with aging, including vision impairment, which may have affected his mood and work. Aging and neurodegenerative disease which often accompanies it, are both associated with depression. Depression is characterised by visual deficits including perception of reduced contrast and colour. Age-related neurological disorders are associated in artists with reduced complexity. Recent advances in imaging and computer technology make it possible to empirically examine changes in artistic style which can contribute to understanding artists’ physical and mental health. Previous studies have identified associations between adverse events in artists’ lives and altered contrast and colour in their self-portraits. In the current study changes in contrast, colour and fractal dimension were measured in the entire corpus of Rembrandt’s painted self-portraits and portraits to determine whether changes in style indicate depression, cognitive decline, or neurological disease and whether differences in style can be detected between self-portraits and portraits of related and unrelated others. Productivity was also examined as an indirect indicator. The results suggest that it is unlikely that Rembrandt suffered from unipolar or bipolar depression, age-related cognitive decline, or neurodegenerative disease. The data are consistent with someone experiencing episodes of low mood associated with normal grieving and adversity followed by resilient recovery. There is evidence of a gradient in saliency and complexity between self-portraits and related and unrelated portraits and of a ‘late’ style identified by leading art historians consistent with macular degeneration.

MTCL2 Is Essential for the Bipolar-to-Multipolar Transition in the Dendrite Extension of Cerebellar Granule Neurons

The dynamic regulation of neuronal polarity is essential for the formation of neural networks during brain development. Primary cultures of rodent neurons recapitulate several aspects of this polarity regulation, providing valuable insights into the molecular mechanisms underlying axon specification, dendrite formation, and neuronal migration. However, the process by which the preexisting bipolarity of migrating neurons is disrupted to form multipolar dendrites remains to be elucidated. In this study, we demonstrate that MTCL2, a microtubule-crosslinking protein associated with the Golgi apparatus, plays a crucial role in this type of polarity transformation exhibited by cerebellar granule neurons (CGNs) in mice of either sex. MTCL2 is highly expressed in CGNs and gradually accumulates in dendrites as the cells develop polarity. MTCL2 knockdown inhibited the bipolar-to-multipolar transition of dendrite extension observed in their differentiation in vitro as well as in vivo. During this transformation, the Golgi apparatus shifts from the base of the preexisting bipolar neurites to the lateral or apical side of the nucleus in the cell body. There, it forms a close association with the microtubule cage that wraps around the nucleus. The resulting upward extension of the Golgi apparatus is tightly coupled with the randomization of its position in the xy plane. Knockdown and rescue experiments demonstrated MTCL2 promotes these changes in the Golgi position in a microtubule- and Golgi-binding activity-dependent manner. These results suggest that MTCL2 promotes the development of multipolar short dendrites by sequestering the Golgi apparatus from the base of the preexisting neurite into the microtubule cage.

Prefrontal and hippocampal microstructural gray matter following cognitive training under moderate hypoxia in mood disorders: a randomized controlled trial

BackgroundCognitive impairment persists during partial or full remission in 50–70% of individuals with mood disorders and impacts daily functioning and clinical prognosis. Preclinical evidence suggests that extended exposure to moderate hypoxia, combined with motor-cognitive learning, may elevate neuroplasticity and improve cognition. In these individuals with remitted mood disorders, we found that cognitive training under repeated moderate normobaric hypoxia improved executive function, and here investigate neurobiological mechanisms.MethodsParticipants with major depressive disorder (MDD) or bipolar disorder (BD) in partial or full remission were randomized to 3 weeks of 3.5-h daily normobaric hypoxia (12% O2) combined with cognitive training five to 6 days per week or treatment-as-usual (TAU). Participants were assessed with cognitive tests and diffusion-weighted MRI at baseline and 1 month after treatment completion (week 8) as part of the ALTIBRAIN trial (ClinicalTrials.gov: NCT06121206). Prefrontal and hippocampal gray matter microstructure were modelled with Neurite Orientation Dispersion and Density Imaging (NODDI).ResultsFifty-seven participants (mean age 39 years, SD: 13, 70% female) with baseline MRI data were included. No significant effects of hypoxia-cognition training vs. TAU on neurite density index (NDI) or orientation dispersion index (ODI) were observed in either the prefrontal cortex or hippocampus (all p-FDR ≥ 0.832). No significant associations were observed between microstructural changes and changes in cognitive function in either region (all p-FDR ≥ 0.721). At baseline, microstructure in both regions was not associated with executive function or global cognition (all p > 0.40).ConclusionThe absence of detectable microstructural changes, despite selective improvements in executive function, indicates that NODDI-derived metrics did not capture structural correlates of the cognitive response to hypoxia-cognition training. Whether this reflects functional neural mechanisms, measurement insensitivity, or the timing of the single follow-up assessment remains to be determined. Future studies should incorporate multiple imaging time points to capture the dynamic trajectories of putative microstructural brain changes.
<![CDATA[Bipolar and spring mania: tips from an expert.]]>