Journal of Psychiatry & Neuroscience最新文献

Background: To study whether there is genetic overlap underlying the risk for schizophrenia spectrum disorders (SSDs) and low intelligence quotient (IQ), we reviewed and summarized the evidence on genetic variants associated with both traits.

Methods: We performed this review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and preregistered it in PROSPERO. We searched the Medline databases via PubMed, PsycInfo, Web of Science and Scopus. We included studies in adults with a diagnosis of SSD that explored genetic variants (single nucleotide polymorphisms [SNPs], copy number variants [CNVs], genomic insertions or genomic deletions), estimated IQ and studied the relationship between genetic variability and both traits (SSD and IQ). We synthesized the results and assessed risk of bias using the Quality of Genetic Association Studies (Q-Genie) tool.

Results: Fifty-five studies met the inclusion criteria (45 case-control, 9 cross-sectional, 1 cohort), of which 55% reported significant associations for genetic variants involved in IQ and SSD. The SNPs more frequently explored through candidate gene studies were in COMT, DTNBP1, BDNF and TCF4. Through genome-wide association studies, 2 SNPs in CHD7 and GATAD2A were associated with IQ in patients with SSD. The studies on CNVs suggested significant associations between structural variants and low IQ in patients with SSD.

Limitations: Overall, primary studies used heterogeneous IQ measurement tools and had small samples. Grey literature was not screened.

Conclusion: Genetic overlap between SSD and IQ supports the neurodevelopmental hypothesis of schizophrenia. Most of the risk polymorphisms identified were in genes relevant to brain development, neural proliferation and differentiation, and synaptic plasticity.

Background: Pediatric obsessive-compulsive disorder (OCD) has been associated with poorer planning in laboratory, school and home settings. It is unclear whether this impairment is a standalone cognitive issue or the result of OCD symptoms. No study has examined the influence of provoked distress on planning performance and neural correlates in pediatric OCD.

Methods: Before and after a symptom provocation task, youth with OCD (n = 23; 9 boys; mean age ± standard deviation 15.1 ± 2.6 years) and matched healthy controls (n = 23) completed the Tower of London task during functional MRI scanning.

Results: During planning, participants with OCD recruited the left superior frontal gyrus to a greater extent than healthy controls after symptom provocation (group × time point interaction; t ₄₄ = 5.22, p < 0.001). In a seeded, region of interest-constrained, functional connectivity analysis, we identified greater connectivity between the left superior frontal gyrus and the right middle frontal gyrus, left precuneus and left inferior parietal lobule in participants with OCD than healthy controls. We also identified greater connectivity between the right amygdala and right medial frontal gyrus in patients with OCD than healthy controls, but only before symptom provocation.

Limitations: The fixed-order design of the study and the number of participants taking medication (n = 20) should be noted.

Conclusion: Participants with OCD demonstrated greater amygdalar-cortical connectivity before symptom provocation, while sustaining greater recruitment and connectivity of task-related planning areas throughout the task. These results suggest that brain activity and connectivity is altered after symptom provocation, in the absence of impaired planning performance.

Background: Schizophrenia is characterized by hallucinations, delusions and disorganized behaviour. Recessive or X-linked transmissions are rarely described for common psychiatric disorders. We examined the genetics of psychosis to identify rare large-effect variants in patients with extreme schizophrenia.

Methods: We recruited 2 consanguineous families, each with patients affected by early-onset, severe, treatment-resistant schizophrenia. We performed exome sequencing for all participants. We checked variant rarity in public databases and with ethnically matched controls. We performed in silico analyses to assess the effects of the variants on proteins.

Results: Structured clinical evaluations supported diagnoses of schizophrenia in all patients and phenotypic absence in the unaffected individuals. Data analyses identified multiple variants. Only 1 variant per family was predicted as pathogenic by prediction tools. A homozygous c.649C > T:p.(Arg217Cys) variant in RGS3 and a hemizygous c.700A > G:p.(Thr234Ala) variant in IL1RAPL1 affected evolutionary conserved amino acid residues and were the most likely causes of phenotype in the patients of each family. Variants were ultra-rare in publicly available databases and absent from the DNA of 400 ethnically matched controls. RGS3 is implicated in modulating sensory behaviour in Caenorhabditis elegans. Variants of IL1RAPL1 are known to cause nonsyndromic X-linked intellectual disability with or without human behavioural dysfunction.

Limitations: Each variant is unique to a particular family's patients, and findings may not be replicated.

Conclusion: Our work suggests that some rare variants may be involved in causing inherited psychosis or schizophrenia. Variant-specific functional studies will elucidate the pathophysiology relevant to schizophrenias and motivate translation to personalized therapeutics.

Background: A hyperactive default mode network (DMN) has been observed in people with major depressive disorder (MDD), and weak DMN suppression has been linked to depressive symptoms. However, whether dysregulation of the DMN contributes to blunted positive emotional experience in people with MDD is unclear.

Methods: We recorded 128-channel electroencephalograms (EEGs) from 24 participants with MDD and 31 healthy controls in a resting state (RS) and an emotion-induction state (ES), in which participants engaged with emotionally positive pictures. We combined Granger causality analysis and data-driven decomposition to extract latent brain networks shared among states and groups, and we further evaluated their interactions across individuals.

Results: We extracted 2 subnetworks. Subnetwork 1 represented a delta (δ)-band (1~4 Hz) frontal network that was activated more in the ES than the RS (i.e., task-positive). Subnetwork 2 represented an alpha (α)-band (8~13 Hz) parietal network that was suppressed more in the ES than the RS (i.e., task-negative). These subnetworks were anticorrelated in both the healthy control and MDD groups, but with different sensitivities: for participants with MDD to achieve the same level of task-positive (subnetwork 1) activation as healthy controls, more suppression of task-negative (subnetwork 2) activation was necessary. Furthermore, the anticorrelation strength in participants with MDD correlated with the severity of 2 core MDD symptoms: anhedonia and rumination.

Limitations: The sample size was small.

Conclusion: Our findings revealed altered coordination between 2 functional networks in MDD and suggest that weak suppression of the task-negative α-band parietal network contributes to blunted positive emotional responses in adults with depression. The subnetworks identified here could be used for diagnosis or targeted for treatment in the future.

Background: We have previously reported activation in reward, salience and executive control regions during functional MRI (fMRI) using an approach-avoidance conflict (AAC) decision-making task with healthy adults. Further investigations into how anxiety and depressive disorders relate to differences in neural responses during AAC can inform their understanding and treatment. We tested the hypothesis that people with anxiety or depression have altered neural activation during AAC.

Methods: We compared 118 treatment-seeking adults with anxiety or depression and 58 healthy adults using linear mixed-effects models to examine group-level differences in neural activation (fMRI) during AAC decision-making. Correlational analyses examined relationships between behavioural and neural measures.

Results: Adults with anxiety or depression had greater striatal engagement when reacting to affective stimuli (p = 0.008, d = 0.31) regardless of valence, and weaker striatal engagement during reward feedback (p = 0.046, d = -0.27) regardless of the presence of monetary reward. They also had blunted amygdala activity during decision-making (p = 0.023, d = -0.32) regardless of the presence of conflict. Across groups, approach behaviour during conflict decision-making was inversely correlated with striatal activation during affective stimuli (p < 0.001, r = -0.28) and positively related to striatal activation during reward feedback (p < 0.001, r = 0.27).

Limitations: Our transdiagnostic approach did not allow for comparisons between specific anxiety disorders, and our cross-sectional approach did not allow for causal inference.

Conclusion: Anxiety and depression were associated with altered neural responses to AAC. Findings were consistent with the role of the striatum in action selection and reward responsivity, and they point toward striatal reactivity as a future treatment target. Blunting of amygdala activity in anxiety or depression may indicate a compensatory response to inhibit affective salience and maintain approach.

Background: Although much is known about cognitive dysfunction in attention-deficit/hyperactivity disorder (ADHD), few studies have examined the pathophysiology of disordered motor circuitry. We explored differences in neurometabolite levels and transcranial magnetic stimulation (TMS)-derived corticomotor representations among children with ADHD and typically developing children.

Methods: We used magnetic resonance spectroscopy (MRS) protocols to measure excitatory (glutamate + glutamine [Glx]) and inhibitory (γ-aminobutyric acid [GABA]) neurometabolite levels in the dominant primary motor cortex (M1) and the supplementary motor area (SMA) in children with ADHD and typically developing children. We used robotic neuronavigated TMS to measure corticospinal excitability and create corticomotor maps.

Results: We collected data from 26 medication-free children with ADHD (aged 7-16 years) and 25 typically developing children (11-16 years). Children with ADHD had lower M1 Glx (p = 0.044, d = 0.6); their mean resting motor threshold was lower (p = 0.029, d = 0.8); their map area was smaller (p = 0.044, d = 0.7); and their hotspot density was higher (p = 0.008, d = 0.9). M1 GABA levels were associated with motor map area (p = 0.036).Limitations: Some TMS data were lost because the threshold of some children exceeded 100% of the machine output. The relatively large MRS voxel required to obtain sufficient signal-to-noise ratio and reliably measure GABA levels encompassed tissue beyond the M1, making this measure less anatomically specific.

Conclusion: The neurochemistry and neurophysiology of key nodes in the motor network may be altered in children with ADHD, and the differences appear to be related to each other. These findings suggest potentially novel neuropharmacological and neuromodulatory targets for ADHD.