Persistent, poor quality competency to stand trial reports: Does training matter?

Consistent with nationwide trends, the number of defendants judicially ordered to the California Department of State Hospitals (DSH) for competency restoration has nearly doubled in recent years. Previous research has shown that the majority of the time, judicial rulings on competency reflect forensic evaluators' opinions. Thus, the quality of competency to stand trial (CST) reports is critical. We examined 388 CST reports from defendants who were ultimately found incompetent to stand trial and admitted to a state hospital for restoration in 2012-2013. We evaluated the reports for adherence to both professional guidelines and current literature on the appropriate conduct of CST evaluations. Consistent with previous studies, our results showed that the reports evidenced overall poor quality and evaluators were largely unable to accurately describe the nature of the mental illness or explain how clinical factors (i.e., diagnoses or symptoms) impacted CST abilities. Notably, we found that experts board certified in psychiatry or psychology produced reports of higher quality. These findings demonstrate the continued poor quality of CST reports and highlight the importance of training. As in previous similar studies, we recommend mandatory training for experts conducting CST evaluations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Economics of decriminalizing mental illness: when doing the right thing costs less.

The United States' criminal justice system has seen exponential growth in costs related to the incarceration of persons with mental illness. Jails, prisons, and state hospitals' resources are insufficient to adequately treat the sheer number of individuals cycling through their system. Reversing the cycle of criminalization of mental illness is a complicated process, but mental health diversion programs across the nation are uniquely positioned to do just that. Not only are these programs providing humane treatment to individuals within the community and breaking the cycle of recidivism, the potential fiscal savings are over 1 billion dollars.

Gender by onset age interaction may characterize distinct phenotypic subgroups in bipolar patients.

OBJECTIVE: Although bipolar disorder (BD) is a common recurrent condition with highly heterogeneous illness course, data are limited regarding clinical implications of interactions between gender and onset age. We assessed relationships between onset age and demographic/illness characteristics among BD patients stratified by gender. METHODS: Demographic and unfavorable illness characteristics, descriptive traits, and clinical correlates were compared in 502 patients from Stanford University BD Clinic patients enrolled in the Systematic Treatment Enhancement Program for BD between 2000 and 2011, stratified by gender, across pre-, peri-, and post-pubertal (<12, 13-16, and >17 years, respectively) onset-age subgroups. RESULTS: Among 502 BD patients, 58.2% were female, of whom 21.9% had pre-pubertal, 30.7% peri-pubertal, and 47.4% post-pubertal onset. Between genders, although demographics, descriptive characteristics, and most clinical correlates were statistically similar, there were distinctive onset-age related patterns of unfavorable illness characteristics. Among females, rates of 6/8 primary unfavorable illness characteristics were significantly higher in pre-pubertal and peri-pubertal compared to post-pubertal onset patients. However, among males, rates of only 3/8 unfavorable illness characteristics were significantly higher in only pre-pubertal versus post-pubertal onset patients, and none between peri-pubertal versus post-pubertal onset patients. LIMITATIONS: Caucasian, insured, suburban, American specialty clinic-referred sample limits generalizability, onset age based on retrospective recall. DISCUSSION: We describe different phenotypic presentations across age at illness onset groups according to gender. Among females and males, peri-pubertal and post-pubertal onset age groups were more different and more similar, respectively. Further investigation is warranted to assess implications of gender-by-onset-age interactions to more accurately delineate distinctive BD phenotypes.

American tertiary clinic-referred bipolar II disorder compared to bipolar I disorder: More severe in multiple ways, but less severe in a few other ways.

BACKGROUND: Prevalence and relative severity of bipolar II disorder (BDII) vs. bipolar I disorder (BDI) are controversial. METHODS: Prevalence, demographics, and illness characteristics were compared among 260 BDII and 243 BDI outpatients referred to the Stanford University BD Clinic and assessed with the Systematic Treatment Enhancement Program for Bipolar Disorder Affective Disorders Evaluation. RESULTS: BDII vs. BDI outpatients had statistically similar prevalence (51.7% vs. 48.3%), and in multiple ways had more severe illness, having significantly more often: lifetime comorbid anxiety (70.8% vs. 58.4%) and personality (15.4% vs. 7.4%) disorders, first-degree relative with mood disorder (62.3% vs. 52.3%), at least 10 prior mood episodes (80.0% vs. 50.9%), current syndromal/subsyndromal depression (52.3% vs. 38.4%), current antidepressant use (47.3% vs. 31.3%), prior year rapid cycling (33.6% vs. 13.4%), childhood onset (26.2% vs. 16.0%), as well as earlier onset age (17.0±8.6 vs. 18.9±8.1 years), longer illness duration (19.0±13.0 vs. 16.1±13.0), and higher current Clinical Global Impression for Bipolar Disorder-Overall Severity (4.1±1.4 vs. 3.7±1.5). However, BDII vs. BDI patients significantly less often had prior psychosis (14.2% vs. 64.2%), psychiatric hospitalization (10.0% vs. 67.9%), and current prescription psychotropic use, (81.5% vs. 93.0%), and had a statistically similar rate of prior suicide attempt (29.5% vs. 32.1%). LIMITATIONS: American tertiary bipolar disorder clinic referral sample, cross-sectional design. CONCLUSIONS: Further studies are warranted to determine the extent to which BDII, compared to BDI, can be more severe in multiple ways but less severe in a few other ways, and contributors to occurrence of more severe forms of BDII.

Rectal prolapse in older children associated with behavioral and psychiatric disorders.

PURPOSE: Rectal prolapse (RP) beyond infancy is challenging, and despite surgical correction, recurrences are not uncommon, suggesting that underlying contributing processes may have a role. This study highlights a previously poorly recognized relationship between RP in older children and behavioral/psychiatric disorders (BPD). We describe the incidence of recurrence and use of behavioral, psychological and physical therapeutic tactics in a multidisciplinary approach to pediatric RP. METHODS: A retrospective 20-year review of RP in children >3 years of age was adopted. Charts were reviewed for gastrointestinal, connective tissue, and BPD conditions, incidence of recurrence, and therapies employed including surgery, behavioral, and physical therapy. RESULTS: 45 patients were included, ranging from 3 to 18 years of age; 29 males. Thirty-seven underwent surgery. Six of the 45 were excluded as they had gastrointestinal or connective tissue conditions placing them at risk for prolapse. Over half (21/39, 53%) had BPD. Slightly more than half of patients had a recurrence, but there was no increased risk in those with associated BPD. While all 21 underwent some therapy for their BPD, over the past 5 years we have enrolled eight of these patients into a program of behavioral and/or physical therapy with all reporting reductions in frequency and severity of prolapse after initiating pelvic floor strengthening, behavior modification, and biofeedback, and avoidance of surgery in three. CONCLUSIONS: This study highlights an important group of pediatric patients with RP that may well benefit from a combination of behavioral therapy, physical therapy as well as surgical intervention to obtain the most optimal outcome.

Childhood-compared to adolescent-onset bipolar disorder has more statistically significant clinical correlates.

BACKGROUND: The strengths and limitations of considering childhood-and adolescent-onset bipolar disorder (BD) separately versus together remain to be established. We assessed this issue. METHODS: BD patients referred to the Stanford Bipolar Disorder Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD Affective Disorders Evaluation. Patients with childhood- and adolescent-onset were compared to those with adult-onset for 7 unfavorable bipolar illness characteristics with replicated associations with early-onset patients. RESULTS: Among 502 BD outpatients, those with childhood- (<13 years, N=110) and adolescent- (13-18 years, N=218) onset had significantly higher rates for 4/7 unfavorable illness characteristics, including lifetime comorbid anxiety disorder, at least ten lifetime mood episodes, lifetime alcohol use disorder, and prior suicide attempt, than those with adult-onset (>18 years, N=174). Childhood- but not adolescent-onset BD patients also had significantly higher rates of first-degree relative with mood disorder, lifetime substance use disorder, and rapid cycling in the prior year. Patients with pooled childhood/adolescent - compared to adult-onset had significantly higher rates for 5/7 of these unfavorable illness characteristics, while patients with childhood- compared to adolescent-onset had significantly higher rates for 4/7 of these unfavorable illness characteristics. LIMITATIONS: Caucasian, insured, suburban, low substance abuse, American specialty clinic-referred sample limits generalizability. Onset age is based on retrospective recall. CONCLUSIONS: Childhood- compared to adolescent-onset BD was more robustly related to unfavorable bipolar illness characteristics, so pooling these groups attenuated such relationships. Further study is warranted to determine the extent to which adolescent-onset BD represents an intermediate phenotype between childhood- and adult-onset BD.

Trends in pharmacotherapy in patients referred to a bipolar specialty clinic, 2000-2011.

OBJECTIVE: To assess mood stabilizer (MS) and second-generation antipsychotic (SGA) prescribing trends in bipolar disorder (BD) outpatients referred to a bipolar disorder specialty clinic over the past 12 years. METHOD: BD outpatients referred to the Stanford University Bipolar Disorder Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation. Prescription rates for MSs and SGAs were compared during the first (2000-2005) and second (2006-2011) six years. RESULTS: Among 597 BD patients (mean±SD age 35.4±8.6 years; 58.1% female; 40.7% Type I, 43.6% Type II, and 15.7% Type Not Otherwise Specified; taking 2.6±1.7 prescription psychotropic medications), lamotrigine, quetiapine, and aripiprazole usage more than doubled, from 14.7% to 37.2% (p<0.0001), 7.2% to 19.7% (p<0.0001), and 3.1% to 10.9% (p=0.0003), respectively, while olanzapine and risperidone use decreased by more than half from 15.0% to 6.6% (p=0.0043), and from 8.7% to 3.8% (p=0.039), respectively. SGA use increased from 34.1% to 44.8% (p=0.013), although MS use continued to be more common (in 65.2% for 2006-2011). Use of other individual MSs and SGAs and MSs as a class did not change significantly. CONCLUSIONS: Over 12 years, in patients referred to a BD specialty clinic, lamotrigine, quetiapine, and aripiprazole use more than doubled, and olanzapine and risperidone use decreased by more than half. Tolerability (for lamotrigine, aripiprazole, olanzapine, and risperidone) more than efficacy (for quetiapine) differences may have driven these findings. Additional studies are needed to explore the relative influences of enhanced tolerability versus efficacy upon prescribing practices in BD patients.

First controlled treatment trial of bipolar II hypomania with mixed symptoms: quetiapine versus placebo.

OBJECTIVES: To compare the efficacy and safety of adjunctive quetiapine (QTP) versus placebo (PBO) for patients with bipolar II disorder (BDII) currently experiencing mixed hypomanic symptoms in a 2-site, randomized, placebo-controlled, double-blind, 8-week investigation. METHODS: Participants included 55 adults (age 18-65 years) who met criteria for BDII on the Structured Clinical Interview for DSM-IV-TR (SCID). Entrance criteria included a stable medication regimen for ≥2 weeks and hypomania with mixed symptoms (>12 on the Young Mania Rating Scale [YMRS] and >15 on the Montgomery Asberg Depression Rating Scale [MADRS] at two consecutive visits 1-3 days apart). Participants were randomly assigned to receive adjunctive quetiapine (n=30) or placebo (n=25). RESULTS: Adjunctive quetiapine demonstrated significantly greater improvement than placebo in Clinical Global Impression for Bipolar Disorder Overall Severity scores (F(1)=10.12, p=.002) and MADRS scores (F(1)=6.93, p=.0138), but no significant differences were observed for YMRS scores (F(1)=3.68, p=.069). Side effects of quetiapine were consistent with those observed in previous clinical trials, with sedation/somnolence being the most common, occurring in 53.3% with QTP and 20.0% with PBO. CONCLUSIONS: While QTP was significantly more effective than PBO for overall and depressive symptoms of BDII, there was no significant difference between groups in reducing symptoms of hypomania. Hypomania improved across both groups throughout the study.

Superior chronic tolerability of adjunctive modafinil compared to pramipexole in treatment-resistant bipolar disorder.

BACKGROUND: Suboptimal outcomes are common in bipolar disorder (BD) pharmacotherapy, and may be mitigated with novel adjunctive agents such as modafinil (a low-affinity dopamine transport inhibitor) and pramipexole (a dopamine D2/D3 receptor agonist). While uncontrolled long-term effectiveness data have been reported for these treatments, reports specifically assessing their comparative acute versus chronic tolerability in BD are lacking. Such information, particularly in relation to discontinuation causes, has substantial relevance, providing initial indications to clinicians which treatment may be better tolerated, and to researchers which agent ought to be assessed in longer-term controlled trials. METHODS: BD outpatients assessed with the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Affective Disorders Evaluation, and followed with the STEP-BD Clinical Monitoring Form, were naturalistically prescribed adjunctive modafinil or pramipexole, and somatic/psychiatric intolerability discontinuation rates were compared. RESULTS: Among 63 BD outpatients (mean ± SD age 43.5 ± 14.3 years, 60.3% female, 42.9% type I, 44.4% type II, 12.7% type not otherwise specified), taking 3.5 ± 1.5 (median 3) concurrent prescription psychotropics, adjunctive modafinil (n=24) for 626.9 ± 863.9 (286) days versus pramipexole (n=39) for 473.7 ± 613.4 (214; p=0.51) days yielded a 26.0% lower somatic/psychiatric intolerability discontinuation rate (12.5% vs. 38.5%; p<0.05), with most of the difference accounted for by more pramipexole somatic intolerability discontinuations, due to nausea and sedation, after the first 12 weeks of treatment. LIMITATIONS: No placebo comparison group. Small sample of predominantly female Caucasian insured outpatients, taking complex concurrent medication regimens. CONCLUSIONS: Further studies are warranted to assess our preliminary observation that modafinil, compared to pramipexole, may be better tolerated for longer-term BD treatment.

Brain-derived neurotrophic factor val66met genotype and early life stress effects upon bipolar course.

BACKGROUND: Gene-environment interactions may contribute to bipolar disorder (BD) clinical course variability. We examined effects of brain-derived neurotrophic factor (BDNF) val66met genotype and early life stress (ELS) upon illness severity and chronicity in adult BD patients. METHODS: 80 patients (43 BD I, 33 BD II, 4 BD not otherwise specified, mean ± SD age 46.4 ± 14.0 years, 63.7% female) receiving open evidence-based and measurement-based care in the Stanford Bipolar Disorders Clinic for at least 12 months underwent BDNF val66met genotyping and completed the Childhood Trauma Questionnaire. BDNF met allele carrier genotype and history of childhood sexual and physical abuse were evaluated in relation to mean prior-year Clinical Global Impressions-Bipolar Version-Overall Severity of Illness (MPY-CGI-BP-OS) score and clinical and demographic characteristics. RESULTS: BDNF met allele carriers (but not non-met allele carriers) with compared to without childhood sexual abuse had 21% higher MPY-CGI-BP-OS scores (3.5 ± 0.7 versus 2.9 ± 0.7, respectively, t = -2.4, df = 28, p = 0.025) and 35% earlier BD onset age (14.6 ± 5.7 versus 22.8 ± 7.9 years, respectively, t = 3.0, df = 27, p = 0.006). Regression analysis, however, was non-significant for a BDNF-childhood sexual abuse interaction. LIMITATIONS: small sample of predominantly female Caucasian insured outpatients taking complex medication regimens; only one gene polymorphism considered. CONCLUSIONS: Between group comparisons suggested BDNF met allele carrier genotype might amplify negative effects of ELS upon BD illness severity/chronicity, although with regression analysis, there was not a significant gene-environment interaction. Further studies with larger samples are warranted to assess whether BDNF met allele carriers with ELS are at risk for more severe/chronic BD illness course.

Enhanced ziprasidone combination therapy effectiveness in obese compared to nonobese patients with bipolar disorder.

OBJECTIVE: To assess longer-term ziprasidone effectiveness in obese and non-obese patients with bipolar disorder (BD). METHODS: Outpatients assessed with the Systematic Treatment Enhancement Program for BD Affective Disorders Evaluation and monitored with the Systematic Treatment Enhancement Program for BD Clinical Monitoring Form received open ziprasidone. RESULTS: Eighty-two patients (39 patients with BD I, 39 patients with BD II, and 4 patients with BD not otherwise specified; mean age, 41.1 years; females, 78.0%; obese, 48.8%) received ziprasidone combined with an average of 3.6 (in 74.4% at least 3) other prescription psychotropics and 1.2 prescription nonpsychotropics. Mean (median) ziprasidone final dose and duration were 134.3 (150) mg/d and 489 (199.5) days, respectively. Ziprasidone yielded in obese compared to nonobese patients less discontinuation (42.5% vs 71.4%, P = 0.01), albeit with a higher rate of addition of subsequent psychotropic medication (62.5% vs 35.7%, P = 0.03). Moreover, obese compared to nonobese patients had a higher rate of shift to final-visit euthymia (27.5% vs 0.0%, P = 0.0002), and more weight loss (-20.7 lbs vs -0.6 lbs, P = 0.001), and obese (but not nonobese) patients had significant improvements in mean Clinical Global Impression-Severity of Illness (decreased 0.6 points; P = 0.03) and Global Assessment of Functioning (increased 3.3 points, P = 0.01) scores. Weight change correlated significantly with Global Assessment of Functioning change (P = 0.047) but not with Clinical Global Impression-Severity of Illness change. Limitations are small sample size and open-label, uncontrolled, observational design. CONCLUSION: Controlled and additional observational studies seem warranted to confirm our preliminary findings suggesting ziprasidone may be more effective in obese compared to nonobese patients with BD already receiving combination pharmacotherapy.

Pilot study of the efficacy of double-blind, placebo-controlled one-week olanzapine stabilization therapy in heterogeneous symptomatic bipolar disorder patients.

BACKGROUND: Olanzapine has demonstrated efficacy in acute mania and bipolar I disorder (BDI) maintenance, but efficacy in brief therapy in more diverse populations, including patients with bipolar II disorder (BDII)/bipolar disorder not otherwise specified (BDNOS) with syndromal/subsyndromal depressive/mood elevation symptoms and taking/not taking concurrent medications remains to be established. METHODS: Fifty adult outpatients (24 BD1, 22 BDII, 4 BDNOS, mean ± SD age 40.8 ± 11.5 years, 28.1% female, already taking 1.1 ± 1.2 [median 1] prescription psychotropics) with 17-item Hamilton Depression Rating Scale (HDRS) ≥10 and/or Young Mania Rating Scale (YMRS) ≥10 and ≤24, were randomized to double-blind olanzapine (2.5-20 mg/day) versus placebo for one week. RESULTS: Among 45 patients with post-baseline ratings, olanzapine (9.0 ± 5.8 mg/day, n = 23) compared to placebo (n = 22) tended to yield greater Clinical Global Impressions-Bipolar Version-Overall Severity of Illness (-1.4 ± 0.9 versus -0.8 ± 1.1, p = 0.08) and Hamilton Anxiety Scale (-7.9 ± 6.3 versus -3.8 ± 6.1, p = 0.07) improvements, and YMRS/HDRS remission rate (47.8% versus 22.7%, p = 0.08), but significantly increased median weight (+2 versus -1 lbs, p = 0.001), and rates of excessive appetite (54.2% versus 22.7%, p = 0.04) and tremor (50.0% versus 9.1% p = 0.004). Number Needed to Treat and 95% Confidence Interval for YMRS/HDRS remission were 4 (1-∞). Numbers Needed to Harm for excessive appetite and tremor were 4 (1-21) and 3 (1-6), respectively. CONCLUSIONS: Olanzapine tended to yield affective improvement and significantly increased weight, appetite, and tremor. Larger controlled studies appear feasible and warranted to assess brief olanzapine therapy in heterogeneous symptomatic bipolar disorder patients.

Open adjunctive ziprasidone associated with weight loss in obese and overweight bipolar disorder patients.

OBJECTIVE: To assess effectiveness and tolerability of open adjunctive ziprasidone for weight loss in obese/overweight patients with bipolar disorders (BD) in diverse mood states, taking weight gain-implicated psychotropic medications. METHOD: 22 obese and three overweight BD patients (20 female; 10 BD-I, 14 BD-II, 1 BD-NOS) with mean ± SD baseline body mass index (BMI) of 31.8 ± 2.5 kg/m2 received ZIP (mean final dose 190 ± 92 mg/day) for mean of 79.2 ± 23.2 days. Weight was assessed at six weekly and three biweekly visits. Subjects entered the study in diverse mood states. At baseline, 21 were taking second-generation antipsychotics, 7 lithium, and 1 valproate, which could be reduced/discontinued at investigators' discretion. RESULTS: Weight and BMI decreased from baseline to endpoint by 4.5 ± 3.4 kg and 1.6 ± 1.2 kg/m2, respectively, at weekly rates of 0.37 kg and 0.13 kg/m2, respectively (all p < 0.00001). 48% of patients had at least 5% weight loss. Obesity rate decreased from 88% to 35% (p < 0.0001). Waist circumference decreased 1.6 inches (p = 0.0001). Overall, mood did not change. Patients with at least moderate baseline mood symptoms experienced significant mood improvement, despite 72% patients decreasing/discontinuing weight gain-implicated psychotropic medications. Seven patients discontinued ZIP early: 3 for weight loss inefficacy, and 1 each for viral gastroenteritis, loss of consciousness, pneumonia with hypomania, and lost to follow up. CONCLUSION: Open adjunctive ziprasidone may be effective for weight loss in obese/overweight BD patients taking weight gain-implicated psychotropic medications. These preliminary data should be considered with caution due to the open uncontrolled design, small sample size, and brief duration.

Toward interaction of affective and cognitive contributors to creativity in bipolar disorders: a controlled study.

BACKGROUND: Enhanced creativity in bipolar disorder patients may be related to affective and cognitive phenomena. METHODS: 32 bipolar disorder patients (BP), 21 unipolar major depressive disorder patients (MDD), 22 creative controls (CC), and 42 healthy controls (HC) (all euthymic) completed the Revised Neuroticism Extraversion Openness Personality Inventory (NEO), the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A), the Myers-Briggs Type Inventory (MBTI); the Barron-Welsh Art Scale (BWAS), the Adjective Check List Creative Personality Scale, and the Figural and Verbal Torrance Tests of Creative Thinking. Mean scores were compared across groups, and relationships between temperament/personality and creativity were assessed with bivariate correlation and hierarchical multiple linear regression. RESULTS: BP and CC (but not MDD) compared to HC had higher BWAS-Total (46% and 42% higher, respectively, p<0.05) and BWAS-Dislike (83% and 93% higher, p<0.02) scores, and higher MBTI-Intuition preference type rates (78% vs. 50% and 96% vs. 50%, p<0.05). BP, MDD, and CC, compared to HC, had increased TEMPS-A-Cyclothymia scores (666%, 451% and 434% higher, respectively, p<0.0001), and NEO-Neuroticism scores (60%, 57% and 51% higher, p<0.0001). NEO-Neuroticism and TEMPS-A Cyclothymia correlated with BWAS-Dislike (and BWAS-Total), while MBTI-Intuition continuous scores and NEO-Openness correlated with BWAS-Like (and BWAS-Total). LIMITATIONS: Relatively small sample size. CONCLUSIONS: We replicate the role of cyclothymic and related temperaments in creativity, as well as that of intuitive processes. Further studies are needed to clarify relationships between creativity and affective and cognitive processes in bipolar disorder patients.

Dorsolateral and dorsomedial prefrontal gray matter density changes associated with bipolar depression.

Mood states are associated with alterations in cerebral blood flow and metabolism, yet changes in cerebral structure are typically viewed in the context of enduring traits, genetic predispositions, or the outcome of chronic psychiatric illness. Magnetic resonance imaging (MRI) scans were obtained from two groups of patients with bipolar disorder. In one group, patients met criteria for a current major depressive episode whereas in the other no patient did. No patient in either group met criteria for a current manic, hypomanic, or mixed episode. Groups were matched with respect to age and illness severity. Analyses of gray matter density were performed with Statistical Parametric Mapping software (SPM5). Compared with non-depressed bipolar subjects, depressed bipolar subjects exhibited lower gray matter density in the right dorsolateral and bilateral dorsomedial prefrontal cortices and portions of the left parietal lobe. In addition, gray matter density was greater in the left temporal lobe and right posterior cingulate cortex/parahippocampal gyrus in depressed than in non-depressed subjects. Our findings highlight the importance of mood state in structural studies of the brain-an issue that has received insufficient attention to date. Moreover, our observed differences in gray matter density overlap metabolic areas of change and thus have implications for the conceptualization and treatment of affective disorders.

Decreased prefrontal, anterior cingulate, insula, and ventral striatal metabolism in medication-free depressed outpatients with bipolar disorder.

This study explored whether cerebral metabolic changes seen in treatment resistant and rapid cycling bipolar depression inpatients are also found in an outpatient sample not specifically selected for treatment resistance or rapid cycling. We assessed 15 depressed outpatients with bipolar disorder (six type I and nine type II) who were medication-free for at least 2 weeks and were not predominantly rapid cycling. The average 28-item Hamilton Depression Scale (HAM-D) total score was 33.9. The healthy control group comprised 19 age-matched subjects. All participants received a resting quantitative 18F-fluoro-deoxyglucose positron emission tomography scan. Data analyses were performed with Statistical Parametric Mapping (SPM5). Analyses revealed that depressed patients exhibited similar global metabolism, but decreased absolute regional metabolism in the left much more than right dorsolateral prefrontal cortex, bilateral (left greater than right) insula, bilateral subgenual prefrontal cortex, anterior cingulate, medial prefrontal cortex, ventral striatum, and right precuneus. No region exhibited absolute hypermetabolism. Moreover, HAM-D scores inversely correlated with absolute global metabolism and regional metabolism in the bilateral medial prefrontal gyrus, postcentral gyrus, and middle temporal gyrus. Analysis of relative cerebral metabolism yielded a similar, but less robust pattern of findings. Our findings confirm prefrontal and anterior paralimbic metabolic decreases in cerebral metabolism outside of inpatients specifically selected for treatment resistant and rapid cycling bipolar disorder. Prefrontal metabolic rates were inversely related to severity of depression. There was no evidence of regional hypermetabolism, perhaps because this phenomenon is less robust or more variable than prefrontal hypometabolism.