Cognitive behavioural therapy for older adults with depressive symptoms living in residential aged care: A pilot study of a systemic treatment model.

Proton magnetic resonance spectroscopy (MRS) has been a useful tool in identifying neurochemical clues towards the pathophysiology of schizophrenia spectrum disorders (SSD), including abnormalities in glutamate, glutamine, and GABA. However, a challenge for the interpretation of MRS data collected with <150 ms echo time (TE) sequences at 3 T is the presence of mobile macromolecules (MM), large molecular weight molecules with shorter transverse relaxation times (T). MMs create broad signals that underlie and overlap with metabolite resonances, which complicate the reliable and accurate quantification of some metabolites. The characteristic pattern of MMs has been shown in animal and human work, and the seven main peaks are commonly labeled by location along the ppm scale (e.g., MM09, MM12, MM14, and MM17) or designated M1–M7 (but see ref. for MM peaks detected at a very high MR field strength). There is still uncertainty regarding the specific constituents of MMs, but preclinical and human brain tissue research identified macromolecules as being mobile cytosolic amino acid proteins (and possibly lipids) such as isoleucine, leucine, valine (M1), threonine, alanine (M2–M3), lysine, arginine (M4 and M7), glutamate, glutamine (M5–M6) (See supplemental Table ). MM signals are commonly regarded as nuisance signals, but they may be functionally significant. MM levels are higher in multiple sclerosis, stroke, tumors, and aging in humans (but see). One 4 T MRS study of drug naïve schizophrenia reported higher MM levels around 3.0 ppm corresponding to M7 in the left anterior cingulate assessed with a standard metabolite sequence and not a metabolite-nulled MM sequence. Interestingly, administration of peripheral lipopolysaccharide (LPS) to induce inflammation causes an increase in M1 that corresponds with microglia activation/changes in healthy mice but not in a transgenic mouse model of Alzheimer’s disease. Changes in MM levels have also been hypothesized to reflect abnormal functioning of the glymphatic system, a system activated during sleep and thought to be responsible for removing waste products from the brain. One study reported that M3 (MM14) and M4 (MM17) were significantly elevated in individuals with normal pressure hydrocephalus, possibly reflecting poor clearance from the brain. Another study reported no differences in M1 (MM09) and M5 (MM20) in the anterior cingulate cortex, dorsolateral prefrontal cortex, and dorsal caudate in people with schizophrenia and healthy controls. However, both studies used a standard metabolite sequence and not a metabolite-nulled MM sequence. A standard metabolite sequence detects metabolites that MMs overlaps with, whereas a metabolite-nulled MM sequence applies an inversion pulse that nulls the metabolite signals and results in an MM spectrum.