Thalamocortical Anatomical Connectivity in Schizophrenia and Psychotic Bipolar Disorder

Abstract

Background: Anatomical connectivity between the thalamus and cortex, including the prefrontal cortex (PFC), is abnormal in schizophrenia. Overlapping phenotypes, including deficits in executive cognitive abilities dependent on PFC-thalamic circuitry, suggest dysrupted thalamocortical anatomical connectivity may extend to psychotic bipolar disorder. We tested this hypothesis and examined the impact of illness stage to inform when in the illness course thalamocortical dysconnectivity emerges.

Methods: Diffusion-weighted imaging data were collected on 70 healthy individuals and 124 people with a psychotic disorder (schizophrenia spectrum = 75; psychotic bipolar disorder = 49), including 62 individuals in the early stage of psychosis. Anatomical connectivity between major divisions of the cortex and thalamus was quantified using probabilistic tractography and compared between groups. Associations between PFC-thalamic anatomical connectivity and executive cognitive abilities were examined using regression analysis.

Results: Psychosis was associated with lower PFC-thalamic and elevated somatosensory-thalamic anatomical connectivity. Follow-up analyses established that lower PFC-thalamic and elevated somatosensory-thalamic anatomical connectivity were present in both schizophrenia and psychotic bipolar disorder. Lower PFC-thalamic anatomical connectivity was also present in early-stage and chronic psychosis. Contrary to expectations, lower PFC-thalamic anatomical connectivity was not associated with impaired executive cognitive abilities.

Conclusions: Altered thalamocortical anatomical connectivity, especially reduced PFC-thalamic connectivity, is a transdiagnostic feature of psychosis detectable in the early stage of illness. Further work is required to elucidate the functional consequences of the full spectrum of thalamocortical connectivity abnormalities in psychosis.

Keywords: anatomical; connectivity; cortex; diffusion; psychosis; thalamus.

Figure 1.

Anatomical connectivity between cortex and thalamus in psychosis. (A) Thalamic anatomical connectivity with the prefrontal cortex (PFC) is reduced in both schizophrenia and psychotic bipolar disorder. In contrast, anatomical connectivity between thalamus and somatosensory cortex is increased in schizophrenia and psychotic bipolar disorder. Occipital cortex connectivity with the thalamus is elevated in schizophrenia compared with both healthy individuals and psychotic bipolar disorder. (B) Within the combined psychotic disorders group (ie, schizophrenia plus psychotic bipolar disorder), PFC anatomical connectivity with the thalamus is reduced in both chronic and early-stage psychosis. Elevated somatosensory anatomical connectivity is present only in early-stage psychosis. See text and supplementary material for complete statistical results. *P < .05.