Effects of acupuncture combined with medication on patients with COVID-19 complicated with bipolar disorder: A protocol of systematic review and meta-analysis.

BACKGROUND: There is growing evidence that coronavirus disease 2019 (COVID-19) can trigger acute episodes of mood disorders or psychotic symptoms. Reports on the treatment of COVID-19-related bipolar disorder (BD) are limited. Our study aimed to investigate the potential for new or recurrent BD due to COVID-19. We qualitatively evaluate clinical treatments (acupuncture combined with medication) and any potential pathophysiological links between infection and BD. METHODS: We searched Embase, PubMed, Cochrane Library, Web of Science and MEDLINE (via Web of Science), Scopus, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure Database, and the Wanfang Database from December 1, 2019, to September 15, 2022, to identify all articles on acupuncture combined with drugs used to treat COVID-19 complicated with bipolar disorders. Two researchers will screen the articles and extract the relevant information. RESULTS: The results will provide a systematic overview of the current evidence on the use of acupuncture combined with drug therapy to treat COVID-19 complicated with bipolar disorder. CONCLUSION: The conclusions of this study will help clarify the effects of acupuncture combined with drug therapy on patients with COVID-19-related BD.

Familial risk for bipolar I disorder is associated with erythrocyte omega-3 polyunsaturated fatty acid deficits in youth with attention-deficit hyperactivity disorder.

Although attention-deficit/hyperactivity disorder (ADHD) and a family history of bipolar I disorder (BD) increase the risk for developing BD, associated pathoetiological mechanisms remain poorly understood. One candidate risk factor is a neurodevelopmental deficiency in omega-3 polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This study investigated erythrocyte EPA+DHA biostatus in psychostimulant-free ADHD youth with ('high-risk', HR) and without ('low-risk', LR) a first-degree relative with BD, and healthy controls (HC). Erythrocyte EPA+DHA composition was determined by gas chromatography, and symptom ratings were performed. A total of n = 123 (HR, n = 41; LR, n = 42; HC, n = 40) youth (mean age: 14.4 ± 2.5 years) were included in the analysis. Compared with HC, erythrocyte EPA+DHA composition was significantly lower in HR (-13%) but not LR (-3%), and there was a trend for HR to be lower than LR (-11%). Both HR and LR differed significantly from HC on all symptom ratings. HR had greater ADHD hyperactivity/impulsive symptom severity, manic symptom severity, and higher parent-reported ratings of internalization, externalization, and dysregulation, compared with LR. ADHD youth with a BD family history exhibit erythrocyte EPA+DHA deficits and a more severe clinical profile, including greater manic and dysregulation symptoms, compared with ADHD youth without a BD family history.

Deficits in auditory and visual steady-state responses in adolescents with bipolar disorder.

BACKGROUND: Many aspects of steady-state responses of the brain remain unclear in bipolar disorder (BD) due to the small number of auditory steady-state response (ASSR) studies and the lack of steady-state visual evoked potential (SSVEP) studies on this complex disorder. Therefore, we assessed the patterns of SSVEP and ASSR in adolescents with BD during an active task to detect possible deficits in these important brain responses compared to normal subjects. METHODS: 27 adolescents with BD and 30 healthy adolescents were assessed in this study. The blinking background of the monitor presented at 15 Hz and the tone signal stimulation at 40 Hz evoked SSVEPs and ASSRs, respectively. The phase and amplitude of the steady-state responses were calculated in the auditory and visual conditions. RESULTS: Patients exhibited a substantially worse performance in the motor control inhibition task during both auditory and visual modalities. Patients showed increased SSVEP amplitude and phase in the frontal region compared to control adolescents. Also, patients exhibited decreased ASSR amplitude in the prefrontal and increased ASSR amplitude in the right-frontal and centro-parietal areas compared to healthy adolescents. CONCLUSIONS: impairments in the production and preservation of SSVEP and ASSR are evident in BD, implicating abnormalities in visual and auditory pathways. Neurophysiological deficits and worse performance in BD adolescents may imply that visual and auditory pathways cannot well transfer the pertinent information from arriving sensory data to the visual and auditory cortices, and the frontal cortex cannot well integrate incoming signals into a unified and coherent perceptual action.

Mood Disorders.

PURPOSE OF REVIEW: This comprehensive review of mood disorders brings together the past and current literature on the diagnosis, evaluation, and treatment of the depressive and bipolar disorders. It highlights the primary mood disorders and secondary neurologic causes of mood disorders that are commonly encountered in a clinical setting. As the literature and our understanding evolve, recent additions to the current literature are important to bring forth to the readers. RECENT FINDINGS: Advancements in clinical medicine have strengthened our understanding of the associations of neurologic and psychiatric diseases. This article highlights the medications frequently used with newly identified mood disorders and the common side effects of these medications. A paradigm shift has moved toward newer treatment modalities, such as the use of ketamine, repetitive transcranial magnetic stimulation, and complementary and alternative medicine. The risks and benefits of such therapies, along with medications, are reviewed in this article. SUMMARY: Mood disorders are extraordinarily complex disorders with significant association with many neurologic disorders. Early identification of these mood disorders can prevent significant morbidity and mortality associated with them. With further expansion of pharmacologic options, more targeted therapy is possible in improving quality of life for patients.

Bright light therapy in the treatment of patients with bipolar disorder: A systematic review and meta-analysis.

The treatment of depressive symptoms of bipolar disorder (BD) has received increasing attention. Recently, some studies have shown that bright light therapy (BLT) seems to be useful for BD depression. This meta-analysis is intended to further elucidate the role of BLT in depressive symptoms in patients with BD. Register of Systematic Reviews PROSPERO: CRD 420191 33642.Randomized controlled trials and cohort studies were retrieved in PubMed, Cochrane Library, EMbase, Web of Science, CINHAL, CBM, CNKI, VIP, and Wanfang from their foundation to March 2020, and other sources as supplement was also retrieved. Data were extracted after strict evaluation of literature quality by two researchers, and Meta-analysis was conducted on literatures that met the inclusion criteria. Meta-analysis was performed using Revman 5.3 software. In total, 12 studies including 847 patients with BD depression were included in our meta-analysis. A meta-analysis found significant differences between BLT and placebo for the following outcomes: (1) depression severity before and after BLT [SMD = -0.43, 95% CI (-0.73,-0.13), P<0.05] in RCT and [SMD = -2.12, 95% CI (-2.3,-1.94), P<0.05] in cohort studies.; (2) the efficacy of duration/timing of light therapy for depressive symptoms in BD [I2 = 85%, SMD = -1.88, 95% CI (-2.04, -1.71),P<0.05] and [I2 = 71%, SMD = -2.1,95% CI(-2.24, -1.96), P<0.05]; (3) the efficacy of different color/color temperatures for depressive symptoms in BD [I2 = 0%, SMD = -0.56, 95% CI (-0.92, -0.19), P<0.05] and [I2 = 97%, SMD = -1.74, 95% CI (-1.99, -1.49), P<0.05].We performed a subgroup meta-analysis of studies that used different light intensities. The results showed that light intensity≥5000 lux significantly reduced the severity of depression. And patients without psychotropic drugs revealed significantly decreased disease severity [I2 = 0%, SMD = -0.6, 95% CI (-1.06,-0.13), P<0.05]. Limitations of the study include studies only assessed short-term effects, and insufficient duration may underestimate adverse reactions and efficacy. Our results highlight the significant efficiency of BLT in the treatment of bipolar depression. Prospective studies with more rigorous design and consistent follow-up.

Efficacy and safety of bright light therapy for manic and depressive symptoms in patients with bipolar disorder: A systematic review and meta-analysis.

AIM: This systematic review and meta-analysis evaluated whether bright light therapy (BLT) is an effective and safe treatment for manic/depressive symptoms and a preventive measure for recurrent mood episodes in patients with bipolar disorder. METHODS: A literature search of major electronic databases was conducted in June 2019, including all published articles up to that date. Two researchers independently selected relevant publications, extracted data, and evaluated methodological quality according to the Cochrane criteria. RESULTS: Six randomized controlled trials (RCT) evaluated the efficacy of BLT for bipolar depression. A meta-analysis found no significant differences between BLT and placebo for the following outcomes: (i) rates of remission from depressive episodes (risk ratio [RR]: 1.81, 95% confidence interval [CI]: 0.43 to 7.64, P = 0.42); (ii) depressive symptom scores (standardized mean difference: -0.25, 95%CI: -0.74 to 0.23, P = 0.30); and (iii) rates of manic switching (RR: 1.00, 95%CI: 0.28 to 3.59, P = 0.26). The sensitivity analysis for studies with low overall indirectness did show a significant antidepressant effect for BLT (RR: 3.09, 95%CI: 1.62 to 5.90, P = 0.006). No RCT investigated the effect of BLT in preventing the recurrence of mood episodes in the euthymic state or in improving manic symptoms in the manic state. No severe adverse events were reported. CONCLUSION: While a meta-analysis was unable to demonstrate the efficacy of BLT for bipolar depression, a sensitivity analysis did show a significant effect. Further well-designed studies are needed to clarify the effectiveness of BLT, not only for the depressive state but also for other states, in the treatment of bipolar disorder.

Synchrony Between Bipolar Mood Cycles and Lunar Tidal Cycles Ended After Initiation of Light Treatment and Treatment of Hypothyroidism.

According to a recent report, mood cycles in a group of patients with rapid cycling bipolar disorder oscillated in synchrony with lunar gravimetric tides. Mood switches in a 67-year-old woman with rapid cycling bipolar II disorder on lithium maintenance treatment were assessed with a χ periodogram and a χ analysis of the mood switches in relation to the lunar tidal cycle. During a period when she was treated with nortriptyline and her thyroid-stimulating hormone levels were elevated, her mood switches had a significant (P<0.05) 29- to 30-day periodicity, and the χ analysis showed that the switches were distributed nonrandomly in relation to the spring-neap lunar tidal cycle (P<0.0001); 14 of 15 switches occurred within 2 days of the spring tides. After nortriptyline was discontinued, thyroid-stimulating hormone levels were normalized with treatment with levothyroxine, and consistent bright light treatment was started, the synchrony between mood cycles and lunar cycles disappeared, and rapid cycling eventually stopped. The possibility that lunar mood cycling is sometimes contingent on antidepressant treatment, decreased thyroid function, and certain types of light-dark cycles needs to be considered in future research on lunar tidal influences on the course of bipolar illness.

Risk of hyperglycemic crisis episode in diabetic patients with bipolar disorder: A nationwide population-based cohort study.

BACKGROUND: Suboptimal management of diabetes can lead to a hyperglycemic crisis episode (HCE), which could be further enhanced in the presence of bipolar disorder (BD) and the prescription of antipsychotics. This study aims to investigate the risk of HCE in diabetic patients with BD. Additionally, the duration of antipsychotic prescription on HCE risk is examined. METHODS: Using the Taiwan National Health Insurance Research Database, 6099 diabetic patients with BD and 24,378 diabetic patients without BD matched by gender, age, index year, and Charlson Comorbidity Index score were enrolled between 1999 and 2010 and followed to the end of 2013. Participants who developed HCE during the follow-up period were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the HCE incidence rate between two groups studied. RESULTS: Diabetic patients with BD were associated with an increased risk of HCE compared with unaffected controls after adjusted for baseline demographics and duration of antipsychotic prescription (3.84 versus 2.71 per 1,000 person-years, HR: 1.41, 95% CI: 1.15-1.71). Also, this study revealed that male gender, more comorbidities, and a longer duration of antipsychotic prescription were potential risk factors for developing HCE. LIMITATIONS: This study only deals with data on the duration of antipsychotic prescription, without showing the effects of different antipsychotics on HCE risk. CONCLUSION: This study highlights the need to pay attention to the risk of HCE in diabetic patients with BD and the importance of careful prescription of antipsychotics to reduce the HCE incident.

Daytime light exposure in daily life and depressive symptoms in bipolar disorder: A cross-sectional analysis in the APPLE cohort.

OBJECTIVES: Controlled artificial daylight exposure, such as light therapy, is effective in bipolar depression, but the association between uncontrolled daytime light and depressive symptoms in bipolar disorder (BD) is unclear. This study investigated the association between daytime light exposure under real-life situations and depressive symptom in patients with BD. METHODS: This cross-sectional study enrolled 181 outpatients with BD. The average daytime light intensity and the total duration of light intensity of ≥1000 lux were recorded over 7 consecutive days using an actigraph that measured ambient light. Depressive symptoms were assessed using Montgomery-Åsberg Depression Rating Scale, and scores of ≥8 points were treated as depressed state. RESULTS: Ninety-seven (53.6%) subjects were depressed state. At higher average daytime light intensity tertiles, the proportion of depressed state was significantly lower (P for trend, 0.003). In multivariable analysis adjusted for age, employment status, age at onset of BD, Young Mania Rating Scale score, bedtime, and physical activity, the highest tertile group in average daytime light intensity suggested a significantly lower odds ratio (OR) for depressed state than the lowest tertile group (OR, 0.33; 95% confidence interval [CI], 0.14-0.75; P = 0.009). Similarly, the longest tertile group in light intensity ≥1000 lux duration was significantly associated with lower OR for depressed state than lowest tertile group (OR, 0.42; 95% CI, 0.18-0.93; P = 0.033). CONCLUSIONS: The findings suggest that greater daytime light exposure in daily life is associated with decreased depressive symptoms in BD.

Use of "Lights" for Bipolar Depression.

PURPOSE: In this review, we will review the background and diagnosis of bipolar disorder (BD); describe the efficacy data and potential circadian and neural mechanisms underlying the effects of bright light for bipolar depression; and discuss the implementation of light therapy in clinical practice. RECENT FINDINGS: To date, morning bright light is the most widely tested form of light therapy for all mood disorders. Clinical trial reports suggest that midday or morning bright light treatment and novel chronotherapeutic interventions are effective for bipolar depression. Mechanisms of response may relate to effects on the circadian system and other changes in neural functioning. Using bright light to manage depressive symptoms in BD is reasonable but also requires concurrent antimanic treatment and careful clinical monitoring for response, safety, and mood polarity switch.

Treating Circadian Rhythm Disruption in Bipolar Disorder.

PURPOSE OF REVIEW: Disruptions in circadian rhythms are believed to underlie the illness course of bipolar disorder (BD). This review evaluates recent studies on the treatment of circadian dysfunction in BD. RECENT FINDINGS: Targeted social rhythm therapy may be useful for bipolar depression though some studies suggest that a non-targeted psychosocial or pharmacological intervention may be just as efficacious. Lithium holds potential for addressing circadian dysfunction in BD. Blue-blocking therapy may be useful for mania and midday bright light therapy may relieve depression. CONCLUSIONS: Psychosocial, pharmacological, and light-based approaches are promising avenues for treating circadian dysfunction in BD.

Hypothalamus enlargement in mood disorders.

OBJECTIVE: The purpose of this study was to determine, in vivo, whether the hypothalamus volume is reduced in patients with mood disorders. METHODS: The cross-sectional study included 20 unmedicated (MDDu) and 20 medicated patients with major depressive disorder, 21 patients with bipolar disorder, and 23 controls. Twenty of the controls were matched to the MDDu. Seven Tesla, T1-weighted magnetic resonance images were acquired and processed using methods specifically developed for high-precision volumetry of the hypothalamus. RESULTS: An overall group difference was observed for the left hypothalamus volume corrected for intracranial volume. Planned contrasts identified that the left hypothalamus was approximately 5% larger in each patient group compared with the control group. A paired t-test with the 20 matched pairs of MDDu and controls and without correction for covariates confirmed the larger left hypothalamus volume in MDDu. CONCLUSIONS: Contrary to our expectations, the hypothalamus volume was increased in patients with uni- and bipolar affective disorders. The effect was left-sided and independent of medication status or statistical correction for covariates. Supported by emerging evidence that the stress response may be related to structural and functional asymmetry in the brain, our finding suggests a crucial role of the hypothalamus in mood disorders.

A potential role for adjunctive omega-3 polyunsaturated fatty acids for depression and anxiety symptoms in recent onset psychosis: Results from a 16 week randomized placebo-controlled trial for participants concurrently treated with risperidone.

Omega-3 treatment studies for multi-episode schizophrenia or clinical high risk for conversion to psychosis states have had variable, and often negative, results. To examine adjunctive omega-3 treatment for recent onset psychosis, participants aged 15-40 years with recent onset schizophrenia-spectrum (n = 46) or bipolar (n = 4) disorders and current psychotic symptoms were treated for 16 weeks with risperidone and randomly-assigned omega-3 (EPA 740 mg and DHA 400 mg daily) or matching placebo. The primary outcome measure was the Brief Psychiatric Rating Scale (BPRS) total score. Mean lifetime antipsychotic exposure was 18.1 days. Length of time in treatment, risperidone dose and number of omega-3/placebo capsules taken did not differ between conditions. Longitudinal analysis of the total BPRS score revealed a trend level (p = 0.0826) treatment effect favoring omega-3 treatment. Lorazepam was an allowed concomitant medication. Among the subgroup (N = 23) who did not receive lorazepam, the treatment effect on BPRS total scores favoring omega-3 was significant (p = 0.0406) and factor scores analyses revealed a substantial decrease in depression-anxiety with omega-3 but no change with placebo (treatment-by-time interaction, p = 0.0184). Motor side effects did not differ between conditions. Analysis of Systematic Assessment for Treatment Emergent Events assessments revealed fewer adverse events overall with omega-3 compared with placebo with the largest differences between conditions (all favoring omega-3) on confusion, anxiety, depression, irritability, and tiredness/fatigue. These results suggest that omega-3 adjuvant treatment is a potential option for depression and anxiety symptoms of people with recent onset psychosis. Further research is needed to confirm this potential. Clinical trial registration: NCT01786239.

Exploring the relationship between fantasy proneness and delusional beliefs in psychosis and non-clinical individuals.

Delusions are a core feature of psychopathology while fantasy proneness (FP) is a trait that describes a predisposition towards fantastical thinking, vivid mental imagery and an overactive imagination. The relationship between FP and delusional experiences has not yet been examined in the literature. The current study hypothesised that FP would be significantly associated with and predict delusion severity as well as the associated delusional distress, preoccupation and conviction. Ninety-five patients with current psychosis (schizophrenia and bipolar I disorder) were assessed for overall delusional severity using the PANSS (clinician-rated) and the Peters Delusions Inventory (PDI; self-report). FP was assessed using the Creative Experiences Questionnaire (CEQ). Forty-six healthy control participants also completed the PDI and CEQ. Significant positive correlations were observed between FP and delusion severity in both groups; and distress, preoccupation and conviction in patients only. Linear regression analyses, controlling for manic and depressive symptoms, revealed that greater FP predicted higher levels of severity, distress, preoccupation, and conviction associated with delusions in patients, and higher severity only in healthy controls. The findings highlight the role of specific cognitive biases in delusional experiences, and empirically support models of unusual belief formation and maintenance.

A Double-Blind, Randomized, Placebo-Controlled Study of Aspirin and N-Acetylcysteine as Adjunctive Treatments for Bipolar Depression.

OBJECTIVE: Neuroinflammation has been implicated in the pathophysiology of bipolar disorder. Some evidence shows that nonsteroidal anti-inflammatory drugs (NSAIDs) have promising antidepressant effects. The antioxidant N-acetylcysteine (NAC) may enhance the effects of NSAIDs. No study has, however, tested the adjunctive therapeutic benefits of an NSAID and NAC in bipolar disorder. METHODS: The sample included 24 medicated patients diagnosed with DSM-IV-TR bipolar disorder who were aged 18-65 years and had a Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 20. Participants were randomly assigned to receive either aspirin (1,000 mg), NAC (1,000 mg), combined aspirin and NAC (1,000 mg each), or placebo. Data were collected between 2013 and 2017. The primary outcome was a ≥ 50% reduction in MADRS scores. Participants completed mood and global functioning questionnaires. They also underwent blood tests prior to and following 8 and 16 weeks of treatment. A Bayesian analytic method was adopted, and posterior probability distributions were calculated to determine the probability of treatment response. RESULTS: Following the first 8-week treatment phase, individuals on treatment with placebo and NAC + aspirin had a similar probability for successful treatment response (about 70%). Following a 16-week treatment period, NAC + aspirin was associated with higher probability of treatment response (67%) compared to placebo (55%), NAC (57%), and aspirin (33%). There was no treatment effect on interleukin-6 and C-reactive protein levels at either 8 or 16 weeks. CONCLUSIONS: The coadministration of NAC and aspirin during a period of 16 weeks was associated with a reduction in depressive symptoms. The adverse effects were minimal. These preliminary findings may serve as a starting point for future studies assessing the efficacy, tolerability, and safety of anti-inflammatory and antioxidant agents in the treatment of bipolar depression. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01797575.

Imagery-Focused Cognitive Therapy (ImCT) for Mood Instability and Anxiety in a Small Sample of Patients with Bipolar Disorder: a Pilot Clinical Audit.

BACKGROUND: Despite the global impact of bipolar disorder (BD), treatment success is limited. Challenges include syndromal and subsyndromal mood instability, comorbid anxiety, and uncertainty around mechanisms to target. The Oxford Mood Action Psychology Programme (OxMAPP) offered a novel approach within a cognitive behavioural framework, via mental imagery-focused cognitive therapy (ImCT). AIMS: This clinical audit evaluated referral rates, clinical outcomes and patient satisfaction with the OxMAPP service. METHOD: Eleven outpatients with BD received ImCT in addition to standard psychiatric care. Mood data were collected weekly from 6 months pre-treatment to 6 months post-treatment via routine mood monitoring. Anxiety was measured weekly from start of treatment until 1 month post-treatment. Patient feedback was provided via questionnaire. RESULTS: Referral and treatment uptake rates indicated acceptability to referrers and patients. From pre- to post-treatment, there was (i) a significant reduction in the duration of depressive episode relapses, and (ii) a non-significant trend towards a reduction in the number of episodes, with small to medium effect size. There was a large effect size for the reduction in weekly anxiety symptoms from assessment to 1 month follow-up. Patient feedback indicated high levels of satisfaction with ImCT, and underscored the importance of the mental imagery focus. CONCLUSIONS: This clinical audit provides preliminary evidence that ImCT can help improve depressive and anxiety symptoms in BD as part of integrated clinical care, with high patient satisfaction and acceptability. Formal assessment designs are needed to further test the feasibility and efficacy of the new ImCT treatment on anxiety and mood instability.

Evidence for differential opioid use disorder in schizophrenia in an addiction treatment population.

Although people diagnosed with schizophrenia are known to have elevated risks of abuse and dependence for nicotine, alcohol, cocaine, and cannabis, it is less clear if schizophrenia is associated with higher rates of opioid use disorders compared to either the general population or individuals with other major psychiatric disorders. Here we examine a large publicly available database from substance abuse treatment centers to compare how frequently patients with schizophrenia report problems with heroin or other opioid drugs compared to other major drugs of abuse. For comparison, the pattern of substance abuse in schizophrenia is contrasted with individuals with major depression, bipolar disorder, and the entire sample of individuals seeking substance abuse treatment. We find that a significantly lower proportion of patients with schizophrenia are reported to have problems with heroin (5.1%) relative to the entire treatment population (18.2%). The schizophrenia sample also had a significantly lower proportion of individuals with a non-heroin opioid problem (7.2%) compared to the entire treatment population (14.8%), patients with depression (23%), and patients with bipolar disorder (17.3%). In contrast, the schizophrenia sample had significantly higher proportions of individuals with problems with alcohol, cocaine, and cannabis relative to the treatment population. Although these data do not allow conclusions on the relative rate of opioid addiction in schizophrenia compared to the general population, the results suggest a discrepancy in patterns of drug choice that may aid our understanding of schizophrenia and substance use comorbidity.

Return to work program efficacy with Self-Regulation Therapy (SRT®): Case study with complex trauma and concurrent disorders.

Background This study shows the efficacy of treating complex cases neurobiologically using Self-Regulation Therapy (SRT®) within the context of return to work goals. Case presentation This is a single case study of a 32-year-old white female. This case study follows a client with concurrent diagnoses of post-traumatic stress disorder (PTSD), bipolar disorder I and substance abuse over the course of 2 years of treatment with SRT®. Using SRT® as primary modality and Likert Scale self-report on the Zettl Scale of Dysregulation, psychiatric medication monitoring and pharmaceutical tracking, this study shows session summaries and progress. Results After six sessions the client was cleared by her psychiatrist for return to work. Her medications were reduced and her post-traumatic symptoms abated. She no longer met diagnostic criteria for PTSD or substance abuse after nine sessions. She returned to work successfully and maintained sobriety and continued symptom reduction. Follow up over a 2-year time period showed consistency and continued improvements in both her professional and her personal life. Conclusions Clients with complex traumatic history with concurrent diagnosis are typically difficult to treat in traditional psychotherapy with limited long-term success. This creates challenges in therapy because the traumas occur during key developmental periods of life. This study shows the efficacy of treating complex cases neurobiologically using SRT®. Using SRT®, clinicians are able to address both developmental and complex trauma to reduce sympathetic arousal in the nervous system providing symptom reduction and even resolution of previous clinical diagnoses.