Table 1.
Summary of major findings from PET brain imaging of depressive disorders for studies cited in the present review.
| Neuronal target | Radioligand | Medication status | Quantification | Diagnostic procedure | Subjects | Regions-of-interest | Outcome | Reference |
|---|---|---|---|---|---|---|---|---|
| Serotonin synthesis | α-[11C]MTrp | Not recently medicated | Patlak graphical method | SCID and HAMD | 25 depressed and 24 healthy | Voxel-based, multi-ROI analysis | More in brain of depressed females than in depressed males | Frey et al. (2010) |
| Serotonin transporter | [11C]McN 5652 | Not recently medicated | Arterial input function and two-tissue compartment model | SCID, HAMD, and BDI | 23 depressed and 43 healthy | Anterior cingulate, amygdala, putamen, hippocampus, midbrain, and thalamus | Less binding in depressed with childhood abuse | Miller et al. (2009b) |
| Serotonin transporter | [11C]DASB | Not recently medicated | Multilinear reference tissue method | SCAN, HAMD, and BDI | 20 healthy twins with or without a co-twin history of mood disorder | Orbitofrontal cortex, dorsolateral prefrontal cortex ventrolateral prefrontal cortex, anterior cingulate, caudate, putamen, thalamus, and midbrain | No reliable correlation between binding and depression scores | Frokjaer et al. (2009) |
| Not recently medicated | Multilinear reference tissue method | SCID | 10 unipolar depressed and 20 healthy | Thalamus | Less binding in depressed | Reimold et al. (2011) | ||
| Not recently medicated | Multilinear reference tissue method | SCID and MADRS | 16 unipolar depressed, 12 bipolar depressed, and 15 healthy | Thalamus, striatum, insula, midbrain, pregenual anterior cingulate cortex, dorsal cingulate cortex, posterior cingulate cortex, and subgenual anterior cingulate cortex | No reliable effect of depression on interaction between thalamic binding and genotype | Laje et al. (2010) | ||
| Anti-Parkinson dopaminergic medication | Logan graphical method with reference tissue | SCID and HAMD | 34 with PD and 10 health | Amygdala, hypothalamus, insula, thalamus, rostral raphe nuclei, caudal raphe nuclei, anterior cingulate cortex, posterior cingulate cortex, prefrontal cortex, caudate nucleus, putamen, and ventral striatum | No reliable difference in binding between depressed PD subjects and healthy | Politis et al. (2010) | ||
| Serotonin type 1A receptor | [11C]WAY-100635 | Not recently medicated | Arterial input function and two-tissue compartment model | SCID and HAMD | 15 remitted depressive, 13 currently depressed, and 51 healthy | Prefrontal cortices, anterior cingulate, body of the cingulate, amygdala, hippocampus, parahippocampal gyrus, insular cortex, temporal cortex, parietal cortex, and occipital cortex | More binding in depressive and depressed than in healthy | Miller et al. (2009a) |
| Not recently medicated | Arterial input function and simplified reference tissue method | SCID, HAMD, and BDI | 32 bipolar depressed and 47 healthy | Prefrontal cortices, anterior cingulate, body of the cingulate, amygdala, hippocampus, parahippocampal gyrus, insular cortex, temporal cortex, parietal cortex, and occipital cortex | No reliable correlation between binding and depression scores | Sullivan et al. (2009) | ||
| Not recently medicated | Arterial input function and simplified reference tissue method | SCID, HAMD, and BDI | 22 depressed and 9 healthy | Amygdala, hippocampus, parahippocampal gyrus, temporal cortex, anterior cingulate, cingulate cortex, prefrontal cortices, insular cortex, occipital cortex, and parietal cortex | More binding in depressed than healthy only for kinetic analysis by arterial input function | Parsey et al. (2010) | ||
| Not recently medicated | Reference tissue method | SCID, HAMD, and BDI | 23 depressed | Voxel-based, multi-ROI analysis | No reliable correlation between binding and therapeutic effect of psychotherapy or SSRI | Karlsson et al. (2010) | ||
| Daily SSRI | Reference tissue method | SCID and HAMD | Nine depressed inpatients and nine healthy | Prefrontal cortex, medial frontal cortex, temporal cortex, parietal cortex, occipital cortex, anterior cingulate, insula, amygdala, hippocampus, and midbrain raphe | No reliable correlation between binding and therapeutic effect of ECT | Saijo et al. (2010a) | ||
| Steady-state drug levels | Reference tissue method | SCID and HAMD | 12 depressed and 12 healthy | Anterior cingulate cortex, orbitofrontal cortex, amygdala, hippocampus, and insula | No reliable correlation between binding and therapeutic effect of ECT | Lanzenberger et al. (2013) | ||
| Antiepileptic drugs and some on SSRI1 | Arterial input function and two-component model | BDI | 40 with temporal lobe epilepsy | Hippocampus | High BDI score correlated with low binding in hemisphere of seizure focus | Theodore et al. (2012) | ||
| Serotonin type 1B receptor | [11C]P943 | Not recently medicated | Multilinear reference tissue method | SCID and MADRS | 10 depressed and 10 healthy | Ventral striatum and ventral pallidum | Less binding in depressed than in healthy | Murrough et al. (2011) |
| Serotonin type 2 receptor | [18F]Setoperone | >1 week antidepressant drug washout | Logan graphical method with reference tissue | SCID and HAMD | 15 treatment-resistant depressed | Voxel-based, multi-ROI analysis | No reliable correlation between binding and therapeutic effect of ECT | Yatham et al. (2010) |
| Dopamine D2/3 receptor | [11C]FLB 457 | Daily SSRI | Reference tissue method | SCID and HAMD | 7 depressed inpatients and 11 healthy | Voxel-based, multi-ROI analysis | No reliable correlation between binding and therapeutic effect of ECT | Saijo et al. (2010b) |
| Multiple monoaminergic receptors | [11C]Mirtazapine | Not recently medicated | Reference tissue method | SCAN, HAMD, and BDI | 17 treatment-resistant depressed and 18 healthy | Cerebral cortices, amygdala, hippocampus, putamen, caudate, and thalamus | Less binding in cortical regions of depressed than healthy | Smith et al. (2009) |
| MAO type A | [11C]Harmine | Not recently medicated | Arterial input function and two-compartment model | SCID and HAMD | 18 remitted depressive, 16 depressed, and 28 healthy | Prefrontal cortex, anterior cingulate cortex, dorsal putamen, ventral striatum, thalamus, anterior temporal cortex, midbrain, and hippocampus | More binding in depressed than in healthy, but no reliable correlation between binding and therapeutic effect of SSRI | Meyer et al. (2009a) |
| Muscarinic type 2 receptor | [18F]FP-TZTP | Not recently medicated | Arterial input function and one-compartment model | SCID and MADRS | 24 unipolar depressed, 16 bipolar depressed, and 25 healthy | Whole brain, anterior, posterior, and dorsal cingulated cortices, amygdala, hippocampus, ventral striatum, lateral orbital cortex, and primary visual cortex | Depending on genotype, less binding in anterior cingulated cortex of bipolar depressed than of unipolar depressed and healthy | Cannon et al. (2011) |
| Nicotinic acetylcholine receptors | 2-[18F]FA-85380 | Anti-parkinson drugs and 3 on antidepressant | Logan graphical method with arterial input function | SCID and BDI | 22 with PD and 9 healthy | Anterior and posterior cingulate cortex, frontal lobe, parietal lobe, temporal lobe, occipital lobe, corpus callosum, hippocampus, amygdala, caudate, putamen, thalamus, midbrain, pons and cerebellum | Low binding in anterior cingulate cortex, left putamen, left midbrain, and right occipital lobe correlated with high BDI scores | Meyer et al. (2009b) |
| GABA type A receptor | [11C]Flumazenil | Initially medication-free, then SSRI in depressed | Logan graphical method with plasma input function | SCID, HAMD, BDI, and MADRS | 11 depressed and 9 healthy | Anterior, ventrolateral, dorsolateral, and orbitomedial prefrontal cortex, anterior and posterior cingulate, medial and lateral temporal lobe, insular, parietal, and occipital areas, cerebellum, hippocampus, putamen, and thalamus | Lower binding in parahippocampal temporal gyri and right superior temporal gyrus in depressed than healthy. SSRI reduced binding in right lateral temporal gyrus and dorsolateral prefrontal cortex of depressed | Klumpers et al. (2010) |
| Phosphodiesterase type IV | [11C]-(R)-Rolipram | Not recently medicated | Logan graphical method with plasma input function | DSM-IV, HAMD, and MADRS | 28 depressed and 25 healthy | Frontal, parietal, lateral temporal, occipital, medial temporal, and anterior cingulate cortices, caudate, putamen, thalamus, and cerebellum | Less binding overall in depressed than healthy, but no correlation between binding and depression scores | Fujita et al. (2012) |
| Amyloid and tau protein | [18F]DDNP | Not recently medicated2 | Logan graphical method with reference tissue | GDS | 23 MCI and 20 non-MCI middle-aged and older subjects | Hippocampus, parahippocampal areas, entorhinal cortex, posterior cingulate, lateral temporal, parietal, and frontal regions | High binding in medial temporal region correlated with high GDS score in non-MCI subjects | Lavretsky et al. (2009) |
| Not recently medicated | Logan graphical method with reference tissue | SCID and HAMD | 20 depressed and 18 healthy | Frontal and parietal cortices, anterior and posterior cingulate, mesial, and lateral temporal lobes | Higher binding in lateral temporal and posterior cingulate regions in depressed than in healthy | Kumar et al. (2011) | ||
| P-glycoprotein | [11C]Verapamil | Antidepressant drugs | Logan graphical method with plasma input function | SCID and HAMD | 14 depressed and 13 healthy | Prefrontal cortex, anterior cingulate cortex, temporal lobes, amygdala, and hippocampus | Less binding in prefrontal cortex and temporal lobes in depressed than in healthy | de Klerk et al. (2009) |
1Personal communication from W. H. Theodore.
2Personal communication from H. Lavretsky.
BDI, Beck self-rating depression inventory; DSM-IV, diagnostic and statistical manual of mental disorders, 4th edition; ECT, electroconvulsive shock therapy; GDS, geriatric depression scale; HAMD, Hamilton depression rating scale; Healthy, no known psychiatric disorder; MADRS, Montgomery–Asberg depression rating scale; MCI, mild cognitive impairment; PD, Parkinson’s disease; ROI, region-of-interest; SCAN, schedules for clinical assessment in neuropsychiatry; SCID, structured clinical interview for the diagnostic and statistical manual of mental disorders.