The implications of hypothalamic abnormalities for schizophrenia

Bernstein, Hans‐Gert; Keilhoff, Gerburg; Steiner, Johann

doi:10.1016/b978-0-12-819973-2.00008-3

Cited by 11 publications

(8 citation statements)

References 110 publications

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“…Arginine-vasopressin is also expressed in SCN neurons. 57 Arginine-vasopressin and oxytocin are known to be involved in the modulation of social interaction, and lower blood plasma levels of these hormones were reported in a study of male patients with SCZ. 58 Reduced level of arginine-vasopressin has been observed in SCZ, although the findings are not consistent, and lower expression of mRNA encoding vasopressin has been reported in the PVN, but not the SON, however, the pathophysiological relevance remains to be clarified.…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic Subunit Volumes in Schizophrenia and Bipolar Spectrum Disorders

Ruggeri,

Nerland,

Mørch-Johnsen

et al. 2024

Schizophrenia Bulletin

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Background The hypothalamus is central to many hormonal and autonomous nervous system pathways. Emerging evidence indicates that these pathways may be disrupted in schizophrenia and bipolar disorder. Yet, few studies have examined the volumes of hypothalamic subunits in these patient groups. We compared hypothalamic subunit volumes in individuals with psychotic disorders to healthy controls. Study Design We included 344 patients with schizophrenia spectrum disorders (SCZ), 340 patients with bipolar disorders (BPD), and 684 age- and-sex-matched healthy controls (CTR). Total hypothalamus and five hypothalamic subunit volumes were extracted from T1-weighted magnetic resonance imaging (MRI) using an automated Bayesian segmentation method. Regression models, corrected for age, age2, sex, and segmentation-based intracranial volume (sbTIV), were used to examine diagnostic group differences, interactions with sex, and associations with clinical symptoms, antipsychotic medication, antidepressants and mood stabilizers. Study Results SCZ had larger volumes in the left inferior tubular subunit and smaller right anterior-inferior, right anterior-superior, and right posterior hypothalamic subunits compared to CTR. BPD did not differ significantly from CTR for any hypothalamic subunit volume, however, there was a significant sex-by-diagnosis interaction. Analyses stratified by sex showed smaller right hypothalamus and right posterior subunit volumes in male patients, but not female patients, relative to same-sex controls. There was a significant association between BPD currently taking antipsychotic medication and the left inferior tubular subunits volumes. Conclusions Our results show regional-specific alterations in hypothalamus subunit volumes in individuals with SCZ, with relevance to HPA-axis dysregulation, circadian rhythm disruption, and cognition impairment.

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Section: Discussionmentioning

confidence: 99%

Hypothalamic Subunit Volumes in Schizophrenia and Bipolar Spectrum Disorders

Ruggeri,

Nerland,

Mørch-Johnsen

et al. 2024

Schizophrenia Bulletin

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show abstract

“…It is worth noting that in this study, we found that increased FT4 level was negatively correlated with adolescence PD. Though many studies explored TH's association with psychotic symptoms [ 25 , 28 , 29 , 38 , 39 ], few were conducted among PD patients. Existing researches elucidated association between hypothyroidism and more frequency of coexisting psychotic phenomenology in depression [ 40 , 41 ], consistent with our study.…”

Section: Discussionmentioning

confidence: 99%

“…TH not only participant in the pathophysiology of depression, but also influence the development of psychotic symptoms. A recent review suggested strong evidence of abnormality in the HPT axis in schizophrenia patients, characterized by psychotic symptoms such as delusion and hallucination [ 25 ]. A 1983 review, a 2021 systematic literature review of published case reports [ 26 ], along with an Expert Opinion [ 27 ] suggest that both hypothyroidism and hyperthyroidism were associated with psychosis [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Association between thyroid function and psychotic symptoms in adolescents with major depressive disorder: A large sample sized cross-sectional study in China

Yang

Zhu

Yue

et al. 2023

Heliyon

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“…The more widespread GPF signal in these fish is consistent with expression in glutamatergic neurons, as well as a few regions with GABAergic neurons (Figure 1). These findings suggest that the SCZassociated variant, rs4129585, likely lies within a TFBS that elicits its regulatory function in glutamatergic neurons and regions of the brain that have been implicated in neurodevelopment and SCZ pathology [53][54][55][56][57][58][59][60][61][62] .…”

Section: A Transcription Factor Binding Site Containing Rs4129585 Dri...mentioning

confidence: 94%

A Functional Schizophrenia-associated genetic variant near theTSNARE1andADGRB1genes

Wahbeh,

Boyd,

Yovo

et al. 2023

Preprint

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Recent collaborative genome wide association studies (GWAS) have identified >200 independent loci contributing to risk for schizophrenia (SCZ). The genes closest to these loci have diverse functions, supporting the potential involvement of multiple relevant biological processes; yet there is no direct evidence that individual variants are functional or directly linked to specific genes. Nevertheless, overlap with certain epigenetic marks suggest that most GWAS-implicated variants are regulatory. Based on the strength of association with SCZ and the presence of regulatory epigenetic marks, we chose one such variant nearTSNARE1andADGRB1, rs4129585, to test for functional potential and assay differences that may drive the pathogenicity of the risk allele. We observed that the variant-containing sequence drives reporter expression in relevant neuronal populations in zebrafish. Next, we introduced each allele into human induced pluripotent cells and differentiated 4 isogenic clones homozygous for the risk allele and 5 clones homozygous for the non-risk allele into neural precursor cells. Employing RNA-seq, we found that the two alleles yield significant transcriptional differences in the expression of 109 genes at FDR <0.05 and 259 genes at FDR <0.1. We demonstrate that these genes are highly interconnected in pathways enriched for synaptic proteins, axon guidance, and regulation of synapse assembly. Exploration of genes near rs4129585 suggests that this variant does not regulateTSNARE1transcripts, as previously thought, but may regulate the neighboringADGRB1, a regulator of synaptogenesis. Our results suggest that rs4129585 is a functional common variant that functions in specific pathways likely involved in SCZ risk.

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The implications of hypothalamic abnormalities for schizophrenia

Cited by 11 publications

References 110 publications

Hypothalamic Subunit Volumes in Schizophrenia and Bipolar Spectrum Disorders

Hypothalamic Subunit Volumes in Schizophrenia and Bipolar Spectrum Disorders

Association between thyroid function and psychotic symptoms in adolescents with major depressive disorder: A large sample sized cross-sectional study in China

A Functional Schizophrenia-associated genetic variant near theTSNARE1andADGRB1genes

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