Navigated and individual α-peak-frequency-guided transcranial magnetic stimulation in male patients with treatment-refractory schizophrenia.

BACKGROUND: Previous electroencephalography (EEG) studies have indicated altered brain oscillatory α-band activity in schizophrenia, and treatment with repetitive transcranial magnetic stimulation (rTMS) using individualized α-frequency has shown therapeutic effects. Magnetic resonance imaging-based neuronavigation methods allow stimulation of a specific cortical region and improve targeting of rTMS; therefore, we sought to study the efficacy of navigated, individual α-peak-frequency-guided rTMS (αTMS) on treatment-refractory schizophrenia. METHODS: We recruited medication-refractory male patients with schizophrenia or schizoaffective disorder in this doubleblind, sham-controlled study. We randomized patients to a 3-week course of either active αTMS or sham stimulation applied to the left dorsolateral prefrontal cortex (DLPFC). We assessed participants with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale (CGI) at baseline and after treatment. We conducted a follow-up assessment with the PANSS 3 months after intervention. RESULTS: We included 44 patients. After treatment, we observed a significantly higher PANSS total score (p = 0.029), PANSS general psychopathology score (p = 0.027) and PANSS 5-factor model cognitive-disorganized factor score (p = 0.011) in the αTMS group than the sham group. In addition, the CGI-Improvement score was significantly higher among those who received αTMS compared with sham stimulation (p = 0.048). LIMITATIONS: The limited number of study participants included only male patients. Depression was not formally evaluated. CONCLUSION: Navigated αTMS to the left DLPFC reduced total, general psychopathological, and cognitive-disorganized symptoms of schizophrenia. These results provide evidence for the therapeutic efficacy of individual α-peak-frequency-guided rTMS in treatment-refractory schizophrenia. CLINICAL TRIAL REGISTRATION: NCT01941251; ClinicalTrials.gov.

Effects of Scheduled Waiting for Psychotherapy in Patients With Major Depression.

The role of nonspecific factors in the outcome of psychotherapy is poorly understood. To study the effects of pretreatment expectancy of scheduled psychotherapy, we examined the effects of an agreed waiting time on the outcome of psychodynamic psychotherapy. Thirty-three treatment-naive outpatients with major depressive disorder were randomly selected to start psychotherapy either directly (DG; n = 17) or after waiting for 6 months (WG; n = 16). In WG, 18% to 60% of the total decline in symptoms took place during the waiting time. After 1 year of active psychotherapy, the anxiety score declined significantly only in WG, and the total length of treatment needed was shorter in WG. No other outcome differences between WG and DG were found. We conclude that scheduled waiting associates with a significant decline in depressive symptoms. Scheduled waiting should be regarded as a preparatory treatment and not as an inert nontreatment control.

Baseline symptom severity predicts serotonin transporter change during psychotherapy in patients with major depression.

AIMS: The role of the serotonin transporter (SERT) in the pathophysiology of depression is unclear and only a few follow-up studies exist. Our aim was to measure changes in SERT availability during psychodynamic psychotherapy in patients with major depression over a follow-up time of 12 or 18 months. METHODS: The patients were studied with iodine-123 labelled 2ß-carbomethoxy-3ß-(4-iodophenyl) serial single-photon emission tomography imaging and clinical rating scales of symptoms. RESULTS: Changes in SERT availability had no correlation with the change of symptoms, but the change of SERT availability during psychotherapy in the midbrain was predicted by the baseline severity of the clinical symptoms measured by the Symptom Checklist Depression Scale and the Symptom Checklist Global Severity Index. With cut-off values applied, it was found that SERT availabilities increased in patients with high baseline symptoms, and decreased in patients with low baseline symptoms. CONCLUSIONS: Together with our earlier finding of decreased SERT in patients with depression, these results indicate a state-dependent and possibly a compensatory role of decreased SERT availability in depression.

The patient-therapist interaction and the recognition of affects during the process of psychodynamic psychotherapy for depression.

The perceptions of patients (n = 25) and their therapists about psychodynamic psychotherapy for depression were assessed during the first treatment year using 23 scales. Patients and therapists independently evaluated the impact of depression on the therapeutic experience of the patients. The estimations of the impact of depression by the patients and therapists were concordant in the majority of the subjects, reflecting mutual tuning and a working alliance. The roles of affects and frustrating subjects in the treatment relationship were evaluated as significantly different by the patients and the therapists. The results highlight the importance of working on the expression of affects in the psychotherapy of depression.

Serotonin-transporter-linked promoter region polymorphism and serotonin transporter binding in drug-naïve patients with major depression.

AIMS: Both the serotonin transporter and its genetic regulation by the serotonin-transporter-linked polymorphic region have a role in the pathophysiology of depression. Most of the previous studies have found no influence of serotonin-transporter-linked polymorphic region allelic variation on serotonin transporter binding in healthy controls or patients with major depression. Due to the inconsistency of the previous findings, we compared single photon emission computed tomography imaging with the serotonin-transporter-linked polymorphic region genotype in patients with major depressive disorder. METHODS: A total of 23 drug-naïve patients with major depressive disorder were genotyped and brain imaged with ([123I])nor-beta-CIT single photon emission computed tomography. The severity of depression was evaluated with the 17-item Hamilton depression rating scale. RESULTS: Depressed patients homozygous for the short allele had lower ([123I])nor-beta-CIT binding in the medial prefrontal cortex, but not in the midbrain, compared with the other genotypes. CONCLUSION: The decreased medial prefrontal cortical serotonin transporter binding in the patients homozygous for the short allele may be linked to altered function of the serotonin-transporter-linked polymorphic region gene expressed in these patients, especially in the medial prefrontal cortex.

Midbrain serotonin and striatum dopamine transporter binding in double depression: a one-year follow-up study.

Data on neurobiological differences between major depression (MD) and double depression (DD) are scarce. We examined the striatum dopamine (DAT) and midbrain serotonin transporter (SERT) binding of [123I] nor-beta-CIT in DD patients (n=8) and compared it to that in MD patients (n=11) and healthy controls (n=19). Drug-naïve patients and controls were imaged by single-photon emission computed tomography at baseline, and the patients also after one year of psychodynamic psychotherapy. Both DD and MD groups had lower midbrain [123I] nor-beta-CIT binding compared with the controls. Baseline 17-item Hamilton Depression Rating Scale (HAM-D-17) scores significantly decreased in both groups after one year of psychotherapy (DD: t=3.55, p=0.009; MD: t=5.86, p<0.001). No differences between the DD and MD groups were observed in age-adjusted baseline striatum or midbrain [123I] nor-beta-CIT binding or its change during psychotherapy. Age-adjusted baseline striatum [123I] nor-beta-CIT binding correlated inversely with the duration of both dysthymia (rho=-0.76, p=0.03) and MD (rho=-0.83, p=0.01) in the DD group. No such finding was observed in the MD group (rho=0.26, p=0.44). Baseline HAM-D-17 did not correlate with the change in striatum or midbrain [123I] nor-beta-CIT binding in either group. In conclusion, our findings suggest that when using midbrain [123I] nor-beta-CIT binding as a marker of SERT binding, no differences are detectable between patients with DD and MD. However, low striatum [123I] nor-beta-CIT binding, a marker of DAT binding, may be associated with a longer illness duration in dysthymia.

Changes in midbrain serotonin transporter availability in atypically depressed subjects after one year of psychotherapy.

BACKGROUND: Psychotherapy is an effective treatment method for depression, but no differences in the psychotherapy response have been found between the subtypes of depression. The effect of psychotherapy on neurotransmitter transporter functions has never been recorded in depressed subjects. METHODS: Depressive outpatients (N=19) received psychodynamic psychotherapy for 12 months. All subjects fulfilled the DSM-IV criteria for depression, and 8 were classified as having atypical depression. The severity of depression was assessed with the 29-item Hamilton Depression Rating Scale (HAM-D-29). Midbrain serotonin transporter (SERT) and striatum dopamine transporter (DAT) densities were recorded using single photon emission computed tomography (SPECT) brain imaging with the [123I]nor-beta-CIT radioligand before and after psychotherapy. RESULTS: Midbrain SERT density significantly increased during psychotherapy in atypicals but not in nonatypicals. There were no changes in the levels of DAT. CONCLUSIONS: The psychotherapy-related SERT elevation of atypically depressed subjects may be due to some unknown adaptive mechanisms inducing an increase in either the levels of SERT or serotonergic nerve terminals and therefore enhancing serotonergic activity and improving mood.

Reduced midbrain serotonin transporter availability in drug-naïve patients with depression measured by SERT-specific [(123)I] nor-beta-CIT SPECT imaging.

Earlier results have indicated that serotonin transporter (SERT) availability is altered in major depression. We examined SERT density with a more serotonin-specific ligand and with a larger number of patients than in previous studies. Twenty-nine antidepressant-naïve patients with major depressive disorder (MDD) and 19 healthy age- and sex-matched controls were studied with SPECT using [(123)I] nor-beta-CIT as a ligand. The patients had a significantly lower (-10%) binding potential in the midbrain region than controls. No correlation with depression severity was found. These findings indicate that SERT availability in the midbrain area is reduced in depression, and that interindividual variation is considerable in both patients and controls.

Midbrain binding of [123I]nor-beta-CIT in atypical depression.

BACKGROUND: Altered serotonin (SERT) and dopamine transporter (DAT) densities have been recorded in major depression. Atypical depression (ATD) has been suggested to be connected to decreased serotonergic transmission, but no studies have been published on the association between brain serotonin transporter density and ATD. METHODS: PATIENTS with depression (n=29) were divided into three groups according to DSM-IV criteria: atypically depressed, melancholic patients, and "undifferentiated" patients. Depressive symptoms were evaluated with the 29-item Hamilton Depression Rating Scale (HAM-D-29). Single photon emission computed tomography (SPECT) with [(123)I]nor-beta-CIT was used to evaluate serotonin transporter density (SERT) in the midbrain and dopamine transporter density (DAT) in the striatum of patients and healthy controls (n=18). RESULTS: All subgroups except those with undifferentiated depression had lower SERT densities compared to controls. No significant differences were found in the densities between the subgroups. Atypical scores of HAM-D-29 were associated with SERT densities in the midbrain (beta=-0.40, t=-2.3, p=0.03), even after adjustment for age, gender and HAM-D-21 scores (beta=-0.39, t=-2.32, p=0.03). CONCLUSIONS: The association between atypical scores of HAM-D-29 and midbrain SERT densities suggests a relationship between serotonergic dysfunction and ATD.

An outcome of psychodynamic psychotherapy: a case study of the change in serotonin transporter binding and the activation of the dream screen.

We explored the outcome of psychodynamic psychotherapy of a female patient with major depression using clinical evaluation and serotonin transporter (SERT) binding assessed with [123I]nor-beta-CIT SPECT. The psychotherapy process was analyzed with special emphasis on the change that was recognized in the dreaming process. The activation of the dream screen in transference seemed to form a turning point during the psychotherapy. Normalization of SERT binding at the midbrain level was found on 12-month follow-up. Major alleviation of depressive symptoms assessed by rating scales was evident only six months after SERT normalization.

Elevated midbrain serotonin transporter availability in mixed mania: a case report.

BACKGROUND: Results obtained from brain imaging studies indicate that serotonin transporter (SERT) and dopamine transporter (DAT) densities are altered in major depression. However, no such studies have been published on current mania or hypomania. CASE PRESENTATION: In this single photon emission computed tomography (SPECT) study with [123I]nor-beta-CIT we present a case with simultaneous symptoms of major depression and hypomania. She had an elevated serotonin transporter availability (SERT) in the midbrain and elevated dopamine transporter availability (DAT) in the striatum, which normalised in a one-year follow-up period during which she received eight months of psychodynamic psychotherapy. CONCLUSIONS: To our knowledge, this is the first report on SERT and DAT associated with mania. In our case the availability of both SERT in the midbrain and DAT in the striatum were elevated at baseline and declined during psychotherapy, while the SERT and DAT of the depressed controls increased during psychotherapy. Symptoms of hypomania in the case were alleviated during psychotherapy. Clinical recovery was also reflected in the Hamilton Depression Rating Scale (HDRS) scores.