The Committee for Treatment Guidelines of Mood Disorders, Japanese Society of Mood Disorders, published a Japanese guideline for the treatment of late‐life depression in 2020. Based on that guideline, the present guideline was developed and revised to incorporate the suggestions of global experts and the latest published evidence. In the diagnosis of late‐life depression, it is important to carefully differentiate it from bipolar disorders, depressive states caused by physical and organic brain disease, drug effects, and dementia, and to determine the comorbidity between late‐life depression and dementia. It is necessary to fully understand the clinical characteristics and psychosocial background of late‐life depression, evaluate the patient's condition, and provide basic interventions based on these factors. Problem‐solving therapy, reminiscence therapy/life review therapy, and behavioral activation therapy, and other forms of psychotherapy can reduce depressive symptoms. In terms of pharmacotherapy, newer antidepressants or non‐tricyclic antidepressants are recommended for late‐life depression, and it is recommended that the efficacy of least the minimal effective dosage should first be determined. Switching antidepressants and aripiprazole augmentation can be used to treatment‐resistant therapy. Electroconvulsive therapy and repetitive transcranial magnetic stimulation have demonstrated usefulness for late‐life depression. Exercise therapy, high‐intensity light therapy, and diet therapy also show some effectiveness and are useful for late‐life depression. Continuation therapy should be maintained for at least 1 year after remission.

Several studies have proved that low-frequency transcranial magnetic stimulation (TMS) of the right dorsolateral prefrontal cortex (DLPFC) showed an antidepressant effect, although its mechanism is still not completely elucidated. The aim of the present study was to clarify the alteration in neuroanatomical function elicited by low-frequency TMS of the right DLPFC in treatment-resistant depression and to detect the difference between responders and nonresponders to TMS. Single-photon emission computed tomography with ^99mTc-ethyl cysteinate dimer was performed in 14 right-handed male patients with treatment-resistant unipolar depression before and after low-frequency TMS of the right DLPFC. Five 60-second 1-Hz trains were applied and 12 treatment sessions were administered within a 3-week period (total pulses, 3,600). The Hamilton Rating Scale for Depression was administered and the regional cerebral blood flow (rCBF) was analyzed using statistical parametric mapping (SPM2). After TMS treatment in 14 patients, the score on the Hamilton Rating Scale for Depression decreased significantly, and considerable decreases in rCBF were seen in the bilateral prefrontal, orbitofrontal, anterior insula, right subgenual cingulate, and left parietal cortex, but no significant increase in rCBF occurred. Additionally, as compared with 8 nonresponders, 6 responders showed significant increases in rCBF at baseline in the left hemisphere including the prefrontal and limbic-paralimbic regions. These results suggest that the antidepressant effect of low-frequency TMS of the right DLPFC is associated with a decrease in rCBF in the limbic-paralimbic regions via the ipsilateral subgenual cingulate, and increased rCBF at baseline in the left hemisphere may be involved in the response to low-frequency TMS treatment.

Aims: Low-frequency transcranial magnetic stimulation (TMS) to the right prefrontal cortex has been shown to be effective in treatment-resistant depression. The aim of the present study was to investigate changes in regional cerebral blood flow (rCBF) after low-frequency right prefrontal stimulation (LFRS), and neuroanatomical correlates of therapeutic efficacy of LFRS in treatment-resistant depression.Methods: Twenty-six patients with treatmentresistant depression received five 60-s 1-Hz trains over the right prefrontal cortex, and 12 treatment sessions were administered during 3 weeks. Brain scans were acquired before and after LFRS using single photon emission computed tomography with 99m Tc-ethyl cysteinate dimer. Severity of depression was assessed on the Hamilton Depression Rating Scale (HDRS).Results: Significant decreases in rCBF after LFRS were seen in the prefrontal cortex, orbitofrontal cortex, subgenual cingulate cortex, globus pallidus, thalamus, anterior and posterior insula, and midbrain in the right hemisphere. Therapeutic efficacy of LFRS was correlated with decreases in rCBF in the right prefrontal cortex, bilateral orbitofrontal cortex, right subgenual cingulate cortex, right putamen, and right anterior insula. Conclusion:The antidepressant effects of LFRS in treatment-resistant depression may be associated with decreases in rCBF in the orbitofrontal cortex and the subgenual cingulate cortex via the right prefrontal cortex.

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High-frequency left prefrontal repetitive transcranial magnetic stimulation (rTMS) has been shown to have efficacy in treatment-resistant depression. However, the effects of rTMS on functional connectivity are still not clear. To examine changes in functional connectivity before and after rTMS, resting EEG of 14 patients with treatment-resistant depression was recorded twice at baseline and at week 4, respectively. The EEG data were analyzed using the standardized low-resolution brain electromagnetic tomography (sLORETA). The results reveal that high-frequency left prefrontal rTMS modulates resting EEG functional connectivity between the left dorsolateral prefrontal cortex and limbic regions, including the subgenual cingulate cortex and parahippocampal gyrus.

Aims:  Low‐frequency right prefrontal repetitive transcranial magnetic stimulation (rTMS) is effective in treating depression, and its antidepressant effects have proven to correlate with decreases in cerebral blood flow (CBF) in the orbitofrontal cortex and subgenual cingulate cortex. However, a predictor of treatment response to low‐frequency right prefrontal rTMS in depression has not been identified yet. The aim of this study was to estimate regional CBF in the frontal regions and investigate the correlation with treatment response to low‐frequency right prefrontal rTMS in depression. Methods:  We examined 26 depressed patients for the correlation between treatment response to rTMS and regional CBF in the frontal regions, by analyzing their brain scans with 99mTc‐ethyl cysteinate dimer before rTMS treatment. CBF in 16 brain regions was estimated using fully automated region of interest analysis software. Two principal components were extracted from CBF in 16 brain regions by factor analysis with maximum likelihood method and Promax rotation with Kaiser normalization. Results:  Sixteen brain regions were divided into two groups: dorsolateral prefrontal cortex (superior frontal, medial frontal, middle frontal, and inferior frontal regions) and ventromedial prefrontal cortex (anterior cingulate, subcallosal, orbital, and rectal regions). Treatment response to rTMS was not correlated with CBF in the dorsolateral prefrontal cortex, but it was correlated with CBF in the ventromedial prefrontal cortex. Conclusion:  These findings suggest that CBF in the ventromedial prefrontal cortex may be a potential predictor of low‐frequency right prefrontal rTMS, and depressed patients with increased CBF in the ventromedial prefrontal cortex may show a better response.

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex is effective in treatment-resistant depression, although its mechanism is still not completely elucidated. To clarify the neuroanatomical alteration of function elicited by rTMS, single photon emission computed tomography (SPECT) with (99m)Tc-ECD was performed on 12 male inpatients with treatment-resistant unipolar depression before and after high-frequency rTMS of the left dorsolateral prefrontal cortex. These results suggest that the manifestation of the antidepressant effect of high-frequency rTMS is associated with changes in the neuroanatomical function of the left dorsolateral prefrontal cortex as well as of the limbic-paralimbic region, including the ipsilateral subgenual cingulate, and the basal ganglia.

The goal of this study was to detect abnormalities in white matter integrity connecting the mediodorsal nucleus of the thalamus and the prefrontal cortex using fiber-tracking technique. Diffusion tensor imaging was acquired in 20 patients with schizophrenia and 20 normal comparison subjects. Fiber tracking was performed on the anterior thalamic peduncle, and the tractography was used to determine the cross-sectional area, mean fractional anisotropy, and standard deviation of fractional anisotropy for every step separately in the right and left hemispheres. Compared with normal subjects, patients showed a significant reduction in the cross-sectional area of the left anterior thalamic peduncle. There were no significant differences for the mean fractional anisotropy bilaterally between the two groups, but significant differences for the standard deviation of fractional anisotropy in both hemispheres. Reduction in the cross-sectional area of the left anterior thalamic peduncle suggests the presence of the failure of left-hemisphere lateralization. In schizophrenic patients a significant increase of the standard deviation of fractional anisotropy raise the possibility that the inhomogeneity of white matter integrity, which is densely or sparsely distributed by site. These findings might provide further evidence for disruption of white matter integrity between the thalamus and the prefrontal cortex in schizophrenia.