Cosyntropin

Reports Net Revenues of $171.8 Million for the Three Months Ended March 31, 2024 RANCHO CUCAMONGA, CA / ACCESSWIRE / May 8, 2024 / Amphastar Pharmaceuticals, Inc., (NASDAQ:AMPH) ("Amphastar" or the "Company") today reported results for the three months ended March 31, 2024. First Quarter Highlights Net revenues of $171.8 million for the first quarter GAAP net income of $43.2 million, or $0.81 per share, for the first quarter Adjusted non-GAAP net income of $55.3 million, or $1.04 per share, for the first quarter Dr. Jack Zhang, Amphastar's President and Chief Executive Officer, commented: "Amphastar's strong first quarter results were led by BAQSIMI ® revenue growth of 22% over what Eli Lilly & Company ("Lilly") reported for the first quarter of 2023. This significant increase demonstrates a strong transition and the potential for continued growth of BAQSIMI ® ." Three Months Ended March 31, 2024 2023 (in thousands, except per share data) Net revenues $ 171,836 $ 140,022 GAAP net income $ 43,177 $ 26,032 Adjusted non-GAAP net income* $ 55,296 $ 32,143 GAAP diluted EPS $ 0.81 $ 0.50 Adjusted non-GAAP diluted EPS* $ 1.04 $ 0.62 ____________________________________ * Adjusted non-GAAP net income and adjusted non-GAAP diluted EPS are non-GAAP financial measures. Please see the discussion in the section entitled "Non-GAAP Financial Measures" and the reconciliation of GAAP to non-GAAP financial measures in Table III of this press release. First Quarter Results Three Months Ended March 31, Change 2024 2023 Dollars % (in thousands) Product revenues: Glucagon $ 28,535 $ 25,696 $ 2,839 11 % Epinephrine 26,110 20,091 6,019 30 % Primatene MIST ® 24,166 23,483 683 3 % BAQSIMI ® 13,843 - 13,843 N/A Lidocaine 12,773 13,646 (873 ) (6 )% Phytonadione 9,973 7,713 2,260 29 % Enoxaparin 7,096 9,867 (2,771 ) (28 )% Naloxone 4,287 4,957 (670 ) (14 )% Other finished pharmaceutical products 29,154 30,557 (1,403 ) (5 )% Total finished pharmaceutical products net revenues $ 155,937 $ 136,010 $ 19,927 15 % API 1,692 4,012 (2,320 ) (58 )% Other revenues 14,207 - 14,207 N/A Total net revenues $ 171,836 $ 140,022 $ 31,814 23 % Changes in net revenues as compared to the first quarter of the prior year were primarily driven by: BAQSIMI ® sales consisting of $13.8 million in sales made by the Company directly to its customers which are recorded as part of Product Revenues, net, and $24.6 million in sales made by Lilly on behalf of the Company under the Transition Services Agreement ("TSA"), which resulted in a net payment to the Company of $14.2 million after deducting cost of sales and other expenses and was recorded in Other Revenues Glucagon sales increased due to a growth in unit volumes, impacting sales by $1.8 million as well as a higher average selling price, impacting sales by $1.1 million as we launched glucagon in Canada Epinephrine and Phytonadione sales increased primarily due to an increase in unit volumes, as a result of other supplier shortages Primatene MIST ® sales increased primarily due to an increase in unit volumes and a higher average selling price Lidocaine sales decreased primarily due to a decrease in unit volumes, as a result of other suppliers returning to their historical distribution levels Enoxaparin and Naloxone sales decreased primarily due to a decrease in unit volumes Other finished pharmaceutical product sales changes were primarily due to: Lower unit volumes of MPA, as our Active Pharmaceutical Ingredient ("API") supplier discontinued making the active ingredient This decrease was partially offset by higher unit volumes of dextrose and sodium bicarbonate caused by other supplier shortages during the quarter Launch of regadenoson in April 2023 API sales decreased primarily due to the timing of customer purchases Three Months Ended March 31, Change 2024 2023 Dollars % (in thousands) Net revenues $ 171,836 $ 140,022 $ 31,814 $ 23 Cost of revenues 81,736 66,182 15,554 24 % Gross profit $ 90,100 $ 73,840 $ 16,260 $ 22 % as % of net revenues 52.4 % 52.7 % Changes in the cost of revenues and the resulting gross margins were primarily driven by: Increase in depreciation and amortization expense related to the acquired BAQSIMI ® assets Increases in labor costs and certain component costs Charges included in cost of revenues to adjust our inventory and related purchase commitments to their net realizable value These factors were partially offset by increased sales of higher-margin products: BAQSIMI ® which was acquired in June 2023 Glucagon, Primatene MIST ® , and epinephrine Regadenoson launched in April 2023 Three Months Ended March 31, Change 2024 2023 Dollars % (in thousands) Selling, distribution, and marketing $ 9,371 $ 7,109 $ 2,262 32 % General and administrative 15,676 13,483 2,193 16 % Research and development 17,043 19,815 (2,772 ) (14) % Non-operating (expenses) income, net (134 ) 136 (270 ) NM Selling, distribution, and marketing expenses increased primarily due to the expansion of our sales and marketing efforts related to BAQSIMI ® General and administrative expenses increased primarily due to an increase in expenses related to BAQSIMI ® Research and development expenses decreased due to the timing of clinical trial expenses, as well as a decrease in materials and supply expenses, primarily related to our insulin and inhalation pipeline products, as a result of a ramp-up in 2023 Cash flow provided by operating activities for the three months ended March 31, 2024, was $55.3 million. Pipeline Information The Company currently has four abbreviated new drug applications ("ANDAs") on the U.S. Food and Drug Administration (the "FDA") targeting products with a market size of over $3 billion, three biosimilar products in development targeting products with a market size of over $7 billion, and four generic products in development targeting products with a market size of over $3 billion. This market information is based on IQVIA data for the 12 months ended March 31, 2024. The Company is developing multiple proprietary products with injectable and intranasal dosage forms. Amphastar's Chinese subsidiary, Amphastar Nanjing Pharmaceuticals, Co., Ltd. ("ANP"), currently has multiple Drug Master Files ("DMFs"), on the FDA and is developing several additional DMFs. Company Information Amphastar is a bio-pharmaceutical company that focuses primarily on developing, manufacturing, marketing, and selling technically-challenging generic and proprietary injectable, inhalation, and intranasal products. Additionally, the Company sells insulin API products. Most of the Company's finished products are used in hospital or urgent care clinical settings and are primarily contracted and distributed through group purchasing organizations and drug wholesalers. More information and resources are available at . Amphastar's logo and other trademarks or service marks of Amphastar, including, but not limited to Amphastar ® , BAQSIMI ® , Primatene MIST ® , REXTOVY TM , Amphadase ® , and Cortrosyn ® , are the property of Amphastar. Non-GAAP Financial Measures To supplement its consolidated financial statements, which are prepared and presented in accordance with U.S. generally accepted accounting principles ("GAAP"), the Company is disclosing non-GAAP financial measures when providing financial results. The Company believes that an evaluation of its ongoing operations (and comparisons of its current operations with historical and future operations) would be difficult if the disclosure of its financial results were limited to financial measures prepared only in accordance with GAAP. As a result, the Company is disclosing certain non-GAAP results, including (i) Adjusted non-GAAP net income (loss) and (ii) Adjusted non-GAAP diluted EPS, which exclude amortization expense, share-based compensation, impairment charges, expenses related to our acquisition of BAQSIMI ® , certain debt issuance costs, legal settlements, and other one-time events in order to supplement investors' and other readers' understanding and assessment of the Company's financial performance because the Company's management uses these measures internally for forecasting, budgeting, and measuring its operating performance. Whenever the Company uses such non-GAAP measures, it will provide a reconciliation of non-GAAP financial measures to their most directly comparable GAAP financial measures. Investors and other readers are encouraged to review the related GAAP financial measures and the reconciliation of non-GAAP measures to their most directly comparable GAAP measures set forth below and should consider non-GAAP measures only as a supplement to, not as a substitute for or as a superior measure to, measures of financial performance prepared in accordance with GAAP. Conference Call Information The Company will hold a conference call to discuss its financial results today, May 8, 2024, at 2:00 p.m. Pacific Time. To access the conference call, dial toll-free (877) 407-0989 or (201) 389-0921 for international callers, ten minutes before the conference. The call can also be accessed on the Investors page on the Company's website Forward Looking Statements All statements in this press release and in the conference call referenced above that are not historical are forward-looking statements, including, among other things, statements relating to our expectations regarding future financial performance and business trends, our future growth, sales and marketing of our products, market size and expansion, product portfolio, product development, the timing of FDA filings or approvals, including the DMFs of ANP, the timing of product launches, acquisitions and other matters related to our pipeline of product candidates, the timing and results of clinical trials, the prospective benefits of the acquisition of BAQSIMI ® , including its potential for continued revenue growth, the success of our integration of BAQSIMI ® , and other future events. These statements are not facts but rather are based on Amphastar's historical performance and our current expectations, estimates, and projections regarding our business, operations, and other similar or related factors. Words such as "may," "might," "will," "could," "would," "should," "anticipate," "predict," "potential," "continue," "expect," "intend," "plan," "project," "believe," "estimate," and other similar or related expressions are used to identify these forward-looking statements, although not all forward-looking statements contain these words. You should not place undue reliance on forward-looking statements because they involve known and unknown risks, uncertainties, and assumptions that are difficult or impossible to predict and, in some cases, beyond Amphastar's control. Actual results may differ materially from those in the forward-looking statements as a result of a number of factors, including those described in Amphastar's filings with the Securities and Exchange Commission, including in our Annual Report on Form 10-K for the year ended December 31, 2023, filed with the SEC on February 29, 2024. In particular, there can be no guarantee that the acquisition of BAQSIMI ® will be beneficial to our business, that any event, change or other circumstance could cause the results of the acquisition and integration of BAQSIMI ® into our product portfolio to differ from Amphastar's expectation, that all or any of the contingent consideration will be payable on the terms described herein or at all, or that Amphastar can reliably predict the impact of BAQSIMI ® on its financial results or financial guidance. You can locate these reports through our website at and on the SEC's website at The forward-looking statements in this release speak only as of the date of the release. Amphastar undertakes no obligation to revise or update information or any forward-looking statements in this press release or the conference call referenced above to reflect events or circumstances in the future, even if new information becomes available or if subsequent events cause our expectations to change. Contact Information: Amphastar Pharmaceuticals, Inc. Bill Peters Chief Financial Officer (909) 476-3416 Table I Amphastar Pharmaceuticals, Inc. Condensed Consolidated Statement of Operations (Unaudited; in thousands, except per share data) Three Months Ended March 31, 2024 2023 Net revenues: Product revenues, net $ 157,629 $ 140,022 Other revenues 14,207 - Total net revenues 171,836 140,022 Cost of revenues 81,736 66,182 Gross profit 90,100 73,840 Operating expenses: Selling, distribution, and marketing 9,371 7,109 General and administrative 15,676 13,483 Research and development 17,043 19,815 Total operating expenses 42,090 40,407 Income from operations 48,010 33,433 Non-operating (expenses) income, net (134 ) 136 Income before income taxes 47,876 33,569 Income tax provision 4,126 6,752 Net income before equity in losses of unconsolidated affiliate 43,750 26,817 Equity in losses of unconsolidated affiliate (573 ) (785 ) Net income $ 43,177 $ 26,032 Net income per share: Basic $ 0.90 $ 0.54 Diluted $ 0.81 $ 0.50 Weighted-average shares used to compute net income per share: Basic 48,212 48,000 Diluted 53,013 51,970 Table II Amphastar Pharmaceuticals, Inc. Condensed Consolidated Balance Sheet (Unaudited; in thousands, except per share data) March 31, December 31, 2024 2023 (unaudited) ASSETS Current assets: Cash and cash equivalents $ 201,148 $ 144,296 Restricted cash 235 235 Short-term investments 88,407 112,510 Restricted short-term investments 2,200 2,200 Accounts receivable, net 138,114 114,943 Inventories 115,494 105,833 Income tax refunds and deposits 784 526 Prepaid expenses and other assets 8,696 9,057 Total current assets 555,078 489,600 Property, plant, and equipment, net 288,523 282,746 Finance lease right-of-use assets 516 564 Operating lease right-of-use assets 31,352 32,333 Investment in unconsolidated affiliate - 527 Goodwill and intangible assets, net 607,064 613,295 Long-term investments 15,163 14,685 Other assets 23,369 25,910 Deferred tax assets 53,252 53,252 Total assets $ 1,574,317 $ 1,512,912 LIABILITIES AND STOCKHOLDERS' EQUITY Current liabilities: Accounts payable and accrued liabilities $ 116,697 $ 93,366 Accrued payments for BAQSIMI ® 128,245 126,090 Income taxes payable 5,857 1,609 Current portion of long-term debt 428 436 Current portion of operating lease liabilities 3,942 3,906 Total current liabilities 255,169 225,407 Long-term reserve for income tax liabilities 6,066 6,066 Long-term debt, net of current portion and unamortized debt issuance costs 594,006 589,579 Long-term operating lease liabilities, net of current portion 28,739 29,721 Other long-term liabilities 17,981 22,718 Total liabilities 901,961 873,491 Commitments and contingencies Stockholders' equity: Preferred stock: par value $0.0001; 20,000,000 shares authorized; no shares issued and outstanding - - Common stock: par value $0.0001; 300,000,000 shares authorized; 60,160,459 and 48,841,343 shares issued and outstanding as of March 31, 2024 and 59,390,194 and 48,068,881 shares issued and outstanding as of December 31, 2023, respectively 6 6 Additional paid-in capital 476,072 486,056 Retained earnings 452,445 409,268 Accumulated other comprehensive loss (8,769 ) (8,478 ) Treasury stock (247,398 ) (247,431 ) Total equity 672,356 639,421 Total liabilities and stockholders' equity $ 1,574,317 $ 1,512,912 Table III Amphastar Pharmaceuticals, Inc. Reconciliation of Non-GAAP Measures (Unaudited; in thousands, except per share data) Three Months Ended March 31, 2024 2023 GAAP net income $ 43,177 $ 26,032 Adjusted for: Intangible asset amortization 6,167 241 Share-based compensation 7,360 6,111 Expenses related to BAQSIMI ® acquisition 1,826 1,217 Income tax provision on pre-tax adjustments (3,234 ) (1,458 ) Adjusted non-GAAP net income $ 55,296 $ 32,143 Adjusted non-GAAP net income per share: Basic $ 1.15 $ 0.67 Diluted $ 1.04 $ 0.62 Weighted-average shares used to compute adjusted non-GAAP net income per share: Basic 48,212 48,000 Diluted 53,013 51,970 Three Months Ended March 31, 2024 Cost of revenue Selling, distribution and marketing General and administrative Research and development Non-operating (expenses) income, net Income tax provision GAAP $ 81,736 $ 9,371 $ 15,676 $ 17,043 $ (134 ) $ 4,126 Intangible asset amortization (6,147 ) - (3 ) (17 ) - - Share-based compensation (2,125 ) (260 ) (3,876 ) (1,099 ) - - Expenses related to BAQSIMI ® acquisition - - - - 1,826 - Income tax provision on pre-tax adjustments - - - - - 3,234 Non-GAAP $ 73,464 $ 9,111 $ 11,797 $ 15,927 $ 1,692 $ 7,360 Three Months Ended March 31, 2023 Cost of revenue Selling, distribution and marketing General and administrative Research and development Non-operating (expenses) income, net Income tax provision GAAP $ 66,182 $ 7,109 $ 13,483 $ 19,815 $ 136 $ 6,752 Intangible asset amortization (211 ) - (30 ) - - - Share-based compensation (1,706 ) (209 ) (3,357 ) (839 ) - - Expenses related to BAQSIMI ® acquisition - - (1,217 ) - - - Income tax provision on pre-tax adjustments - - - - - 1,458 Non-GAAP $ 64,265 $ 6,900 $ 8,879 $ 18,976 $ 136 $ 8,210 SOURCE: Amphastar Pharmaceuticals, Inc. 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引言在当今社会，孤独被认为是一个日益严重的公共卫生问题，其对个人身心健康的负面影响已引起全球范围内科学家和医疗专业人士的广泛关注。孤独感并不仅仅是缺乏社会互动的简单体验，而是一种深层的、主观的不满足感，与人们的社交关系质量和深度密切相关。研究表明，长期的孤独状态不仅会加剧抑郁(depression)、痴呆(dementia)等精神健康问题，还与心血管疾病(cardiovascular disease)、免疫系统功能障碍(immune-system dysfunction)等多种身体健康问题有关。这一问题在全球范围内都非常普遍，根据Meta和盖洛普(Gallup)公司联合进行的一项调查显示，大约有四分之一的成年人感到非常或相当孤独。随着科学研究的深入，人们开始揭示孤独感如何通过神经机制影响人体健康。认知神经科学家正在探索孤独感如何改变大脑的多个方面，从大脑体积到神经元之间的连接。这些早期研究结果揭示了一个复杂的画面，即孤独感可能通过多种途径影响大脑功能，从而对健康产生广泛的影响。值得注意的是，孤独感不仅是一个个人经历的问题，它还与社会经济因素紧密相关。在美国，黑人和西班牙裔成年人以及年收入低于50,000美元的人群的孤独感发生率比其他人群至少高出10个百分点。此外，COVID-19大流行可能通过迫使人们隔离数月甚至数年，加剧了孤独感的问题。虽然老年人长期被认为是孤独感最严重的群体，但数据显示，年轻成年人的孤独感实际上更高，这突显了跨代际的孤独问题。对于解决孤独感的途径，研究者们提出了多种策略，从增加社交活动的机会到直接通过运动等方式触及孤独感的神经机制。例如，有研究发现，每小时步行4-5公里可以完全扭转与孤独感相关的低落情绪，特别是那些默认网络(default network)连通性较高的人，这是一项有趣的发现，因为默认网络也与抑郁(depression)有关。（4月3日 Nature “Why loneliness is bad for your health”）孤独对身心健康的影响心血管疾病与孤独：隐藏的联系孤独感与心血管疾病(cardiovascular disease)之间的联系是一个复杂而微妙的领域，近年来的研究揭示了两者之间存在的潜在联系。心血管疾病是一类影响心脏和血管健康的疾病，包括冠状动脉疾病(coronary artery disease)、高血压(hypertension)和中风(stroke)等。孤独感作为一种深层的、主观感受到的社会隔离状态，已被证明与心血管疾病的风险增加有关。首先，孤独感会导致慢性压力(chronic stress)的增加，这是连接孤独感与心血管疾病的一个重要环节。长期的压力状态会导致应激激素(stress hormone)，如皮质醇(cortisol)的水平升高，这些激素的持续高水平会对心血管系统产生负面影响，包括促进动脉硬化(arteriosclerosis)、增加血压和降低心脏功能。其次，孤独感还与不良的生活方式选择相关，如吸烟(smoking)、过度饮酒(excessive alcohol consumption)和缺乏体育锻炼(lack of physical exercise)。这些行为都是心血管疾病的已知风险因素，它们可以通过孤独感引起的情绪和行为改变而加剧。此外，孤独感还可能通过影响人体的免疫系统(immune system)功能来间接影响心血管健康。研究表明，孤独感与免疫系统的低下功能有关，这可能增加炎症(inflammation)的水平，而炎症被认为是心血管疾病发展的关键因素之一。神经机制方面的研究也为理解孤独感与心血管疾病之间的联系提供了线索。孤独感被发现与大脑的某些区域活动改变有关，这些改变可能影响到人的应对压力的能力以及社交互动的认知处理。例如，大脑的默认网络(default mode network)与自我反思和社会认知有关，孤独感可能通过影响这一网络的功能，间接影响到心血管健康。认知功能下降：孤独与痴呆症的关系孤独感与痴呆症(dementia)之间的关系是当前神经科学和心理学领域的一个重要研究话题。痴呆症是一种以认知功能严重下降为特征的疾病，常见类型包括阿尔茨海默病(Alzheimer's disease)和血管性痴呆(vascular dementia)。研究表明，孤独感不仅是痴呆症患者常见的情感问题，而且还可能是痴呆症发生和发展的一个风险因素。首先，孤独感被发现与大脑结构和功能的变化有关，这些变化与认知下降相关。例如，孤独感与大脑默认网络(default mode network)的改变有关，该网络在自我相关思维和记忆回忆中发挥作用。孤独感还与大脑灰质(grey matter)体积的减少有关，灰质包含了大量的神经细胞，其体积的减少可能影响认知功能。其次，孤独感可导致慢性应激(chronic stress)反应，从而引起一系列生理变化，包括炎症水平的增加和应激激素(stress hormones)如皮质醇(cortisol)水平的上升。这些生理变化被认为是痴呆症发展的潜在机制。特别是，高水平的炎症和应激激素可能会损害大脑神经细胞，加速大脑老化过程，从而促进痴呆症的发展。研究还发现，孤独感与神经退行性疾病(neurodegenerative diseases)的生物标志物(biomarkers)有关。例如，一项研究表明，感到孤独的人更有可能在大脑中积累与阿尔茨海默病相关的β-淀粉样蛋白(β-amyloid)斑块，这是该疾病的主要生物标志之一。此外，社交互动被认为对认知功能具有保护作用，因为它可以提供认知刺激，促进神经可塑性(neuroplasticity)和认知储备(cognitive reserve)的建立。孤独感减少了社交互动的机会，可能会削弱这种保护作用，从而增加痴呆症的风险。情绪障碍：从孤独到抑郁研究表明，孤独感与抑郁症之间存在密切联系。抑郁症患者往往感到孤独，反之亦然。孤独感可能导致抑郁情绪的加剧，而抑郁症患者可能因其病情而难以与他人建立和维持社交联系，从而加深了他们的孤独感。此外，孤独感还与心理健康的其他方面有关，如自杀风险的增加。此外，孤独感和抑郁症都与大脑的生理变化有关。例如，一项研究发现，孤独感与大脑默认网络(default network)的改变有关，这一网络在个体不参与特定任务时处于活跃状态，并且与自我反省有关。这可能解释了为什么感到孤独的人在社交情境中的感知和反应与非孤独的人不同，这种差异可能进一步导致社交隔阂，加剧孤独感。孤独感还会影响大脑对奖赏的处理方式，与多巴胺("dopamine")系统有关，这是一种与愉悦感和奖赏相关的神经递质。孤独和抑郁症患者可能对社交互动和其他奖赏性刺激的反应减弱，这进一步加剧了他们的症状。免疫系统受损：孤独如何降低身体抵抗力首先，孤独感可以增加应激激素，特别是皮质醇(cortisol)的水平。皮质醇是一种重要的应激激素，短期内可以帮助身体应对压力，但长期高水平的皮质醇会抑制免疫系统，降低身体对感染的抵抗力。长期的孤独感导致的慢性应激状态可以使个体更容易受到病原体的侵袭。其次，孤独感还会影响促炎和抗炎细胞因子的平衡。细胞因子(cytokines)是一组小蛋白，负责在身体内传递免疫信号。孤独感会导致促炎细胞因子的增加和抗炎细胞因子的减少，从而增加慢性炎症的风险。慢性炎症与多种疾病，如心血管疾病、糖尿病和某些类型的癌症有关。此外，孤独感还可能通过影响睡眠质量来削弱免疫系统。良好的睡眠对维持正常的免疫功能至关重要。孤独感可能导致睡眠障碍，如难以入睡、睡眠质量差和睡眠中断，这些问题会进一步损害免疫系统的效能。值得注意的是，孤独感导致的免疫系统受损并非独立发生，它与心理压力、慢性炎症和其他健康风险因素相互作用，形成一个复杂的网络，共同降低了身体的抵抗力。因此，解决孤独感和提高社交支持不仅对改善心理健康至关重要，也是提升身体健康和增强免疫力的关键策略。孤独的生理和心理机制大脑如何响应孤独：神经科学的视角大脑区域前扣带皮层(Precuneus)和脑岛(Insula): 这些区域在处理社会排斥和情感痛苦时特别活跃。孤独感增加时，这些区域的活动也会增加，表明个体在经历社会排斥时的情绪痛苦。海马体(Hippocampus): 与记忆和情绪调节有关。长期的孤独感可能影响海马体的结构和功能，从而影响情绪和记忆。前额叶皮层(Prefrontal Cortex): 负责复杂的认知行为，如规划、决策和社会行为。孤独感可能会导致前额叶皮层功能的改变，影响决策和社会交往能力。神经递质的作用多巴胺(Dopamine): 与奖励和快感机制相关，孤独感可能会影响大脑中多巴胺的释放，导致奖励感知的下降。皮质醇(Cortisol): 通常被称为“应激激素”，长期孤独可能会导致皮质醇水平升高，这与压力反应有关。血清素(Serotonin): 影响情绪和社交行为，孤独感可能会扰乱血清素系统，导致情绪问题，如抑郁。孤独与慢性压力：从生理角度理解孤独生理应激反应孤独感可以被视为一种社会性的应激源，能够触发身体的应激反应。这种应激反应主要通过下丘脑-垂体-肾上腺轴(Hypothalamic-Pituitary-Adrenal Axis, HPA Axis)来调控，是身体对压力做出反应的主要系统之一。下丘脑(Hypothalamus): 检测到压力信号后，下丘脑会释放促肾上腺皮质激素释放因子(Corticotropin-Releasing Factor, CRF)。垂体(Pituitary Gland): CRF刺激垂体分泌腺垂体促肾上腺皮质激素(Adrenocorticotropic Hormone, ACTH)。肾上腺(Adrenal Glands): ACTH促使肾上腺分泌皮质醇(Cortisol)，一个主要的应激激素，它影响许多身体系统的功能。皮质醇的角色皮质醇是体内的主要应激激素，对应激反应和能量代谢有着重要作用。在短期内，皮质醇的增加有助于应对压力，提高警觉性和能量水平。然而，长期的慢性压力——如持续的孤独感——会导致皮质醇水平持续升高，从而引发一系列负面健康后果：免疫系统抑制: 长期的高皮质醇水平会抑制免疫系统，降低抵抗感染的能力。代谢异常: 长期升高的皮质醇水平与肥胖、2型糖尿病和心血管疾病有关。神经系统影响: 高皮质醇水平可以影响大脑功能，尤其是影响记忆和认知功能的海马体。自主神经系统的调节孤独感还影响自主神经系统，特别是交感神经系统(Sympathetic Nervous System)和副交感神经系统(Parasympathetic Nervous System)的平衡。交感神经系统的激活是“战斗或逃跑”反应的一部分，而副交感神经系统则负责“休息和消化”反应。慢性孤独感可以导致交感神经系统的过度激活和副交感神经系统的抑制，从而增加心率、血压和炎症水平，长期而言可能导致心血管疾病。炎症反应持续的孤独感和慢性压力还会促进炎症反应。炎症是身体对伤害或感染的自然反应，但慢性炎症可以对身体产生负面影响。研究发现慢性压力，包括孤独感，会增加炎症性细胞因子(Pro-inflammatory Cytokines)的水平，如肿瘤坏死因子-α(Tumor Necrosis Factor-alpha, TNF-α)和白介素-6(Interleukin-6, IL-6)。这种长期的炎症状态与多种疾病的发展有关，包括心血管疾病、2型糖尿病、某些癌症类型和神经退行性疾病。社会和心理因素：孤独的触发点社会隔离物理隔离: 这是最直接的孤独源，指的是个体在物理空间上与他人的分离，如远离家庭、朋友或社区。社交网络的质量和数量: 社交网络的规模较小或质量较低（缺乏深层次、有意义的连接）可能导致孤独感。人际关系的质量社会支持的缺乏（Lack of Social Support）: 人际关系中缺乏情感支持、认同感或归属感，可能导致孤独感。人际冲突（Interpersonal Conflict）: 家庭、工作或朋友圈中的冲突和紧张关系也是导致孤独的重要社会因素。心理特征自我意识（Self-awareness）: 过度的自我意识和对他人评价的高度敏感可能导致社交焦虑，从而增加孤独感。抑郁和焦虑（Depression and Anxiety）: 这些心理状态本身可能导致孤独感，也可能是孤独感的结果，形成一个恶性循环。社会身份和归属感少数群体（Minority Groups）: 属于少数群体的个体可能由于种族、性取向、性别身份或其他社会身份而感到孤立或边缘化。文化和语言障碍（Cultural and Language Barriers）: 移民和难民可能因文化和语言差异而难以融入新社区，从而感到孤独。生活事件和变化重大生活事件（Significant Life Events）: 如亲人去世、失业或离婚等事件可能导致人际关系的丧失，增加孤独感。生活阶段变化（Life Stage Transitions）: 比如从学校毕业、退休或搬家，这些转变可能打破旧有的社交模式，产生孤独感。技术和社交媒体社交媒体的使用: 虽然社交媒体提供了与他人联系的方式，但过度依赖虚拟交流可能导致现实生活中的社交技能退化和人际关系的淡化，从而增加孤独感。数字孤立（Digital Isolation）: 过度使用数字设备可能减少面对面的社交互动，导致实际的社交隔离。态度和认知社交信念（Social Beliefs）: 对社交互动和人际关系持有消极信念（如“没有人能理解我”）可以导致回避社交行为，从而增加孤独感。认知扭曲（Cognitive Distortions）: 如过度概括、黑白思维等，可能导致对社交场合的错误解读，加剧孤独感。身体健康状况慢性疾病和残疾（Chronic Illness and Disability）: 这些健康状况可能限制个体的社交活动能力，导致社交圈缩小，增加孤独感。感官障碍（Sensory Impairments）: 如听力或视力损失，可能使个体难以进行正常的社交交流，导致孤独。经济和职业因素职业孤立（Occupational Isolation）: 某些职业可能要求个体长时间独自工作，或者工作环境不利于建立同事间的亲密关系。经济困难（Economic Hardship）: 财务压力可能导致个体无法参与某些社交活动，感到与社会脱节。环境因素居住环境（Living Environment）: 居住在人口稀少或社区支持较弱的地区，可能导致社交机会减少，增加孤独感。社区和社会参与度（Community and Societal Engagement）: 社区参与度低或社会归属感不强的个体可能更容易感到孤独。应对孤独的策略与方法社交活动与群体互动：缓解孤独的有效途径社交活动和群体互动是缓解孤独感的有效方法。孤独与社会隔离不同，孤独是个体对社交关系满意度的主观感受。增加社交活动的途径之一是通过建设具有公共区域的社区来促进人与人之间的交流。此外，有研究通过运动这一直接方式来触及孤独感背后的神经机制。例如，步行4-5公里能够完全逆转与孤独感相关的低落情绪。这表明运动不仅有助于改善身体健康，还有助于提高社交互动的频率和质量。具体来说，运动可能通过打断与自我反思相关的神经过程，将活动转移到与身体活动相关的大脑区域，从而帮助人们摆脱消极思维的循环。这也解释了为什么具有较高默认网络连接性的人，即那些更容易沉浸于内心思考的人，会从运动中获得更多益处。心理干预与治疗：专业角度如何帮助心理干预和治疗通过不同的策略和技术，帮助个体识别和处理孤独感背后的根本原因，促进更健康的社交行为和心理状态。一种常见的心理干预方法是认知行为疗法(Cognitive Behavioral Therapy, CBT)。CBT 帮助个体识别和改变导致孤独感的负面思维模式和行为，鼓励建立积极的社交互动。此外，CBT还能提高个体应对社交情境的技能，减少社交焦虑(social anxiety)，从而降低孤独感。心理支持小组(psychological support groups)也是一种有效的干预方式，它提供了一个共享经验、相互支持的平台。在小组中，个体可以学习到他人的应对策略，感受到归属感(belongingness)和社会支持(social support)，这对减轻孤独感至关重要。除了面对面的干预和治疗，数字心理干预(digital psychological interventions)——如在线心理治疗(online therapy)和基于应用的自助工具(app-based self-help tools)——提供了更灵活、更易于访问的选择。这些工具可以帮助用户在日常生活中实时应对孤独感，增强社交技能，并提高情绪管理能力。政策与公共健康策略：构建更具包容性的社会首先，公共空间的设计和城市规划(Urban Planning)在促进社交互动和减少孤独感方面扮演着关键角色。通过创建更多公共聚集地如公园、社区中心(Community Centers)和行人友好区域，政策可以鼓励社区成员之间的自然互动，增加社交机会。其次，社会支持计划(Social Support Programs)是减轻特定群体孤独感的重要政策工具。这些计划可以针对老年人、残疾人、低收入家庭等易感群体，提供定制化的服务和活动，以促进他们的社会参与和归属感。在教育政策(Educational Policies)方面，学校和教育机构可以通过培养学生的社交技能(Social Skills)和情感智力(Emotional Intelligence)来减少孤独感。这包括教育课程中关于情感健康(Emotional Health)和人际交往(Interpersonal Communication)的内容，以及鼓励学生参与团队活动和社交俱乐部。健康政策(Health Policies)也应考虑孤独感对个体健康的影响。提供心理健康服务(Mental Health Services)和资源，让人们更容易获得支持，特别是在识别和治疗与孤独相关的健康问题，如抑郁症(Depression)和焦虑症(Anxiety)方面。工作场所政策(Workplace Policies)也是减轻成年人孤独感的重要领域。通过促进更灵活的工作安排(Flexible Working Arrangements)，增加团队建设活动(Team-building Activities)，和创建更加开放和支持性的工作环境(Open and Supportive Work Environment)，雇主可以帮助员工建立更强的同事间关系和社会网络。最后，公共政策(Public Policy)需要考虑到数字包容性(Digital Inclusion)，确保所有人群，特别是较不熟悉技术的老年人，都能访问和利用连接技术(Connective Technologies)，如社交媒体(Social Media)和在线社区(Online Communities)，以减轻孤独感。Q&A孤独与社会隔离有什么不同？孤独与社会隔离是两个相关但不同的概念。社会隔离是指一个人在物理上与他人隔离，缺乏有意义的社会联系。而孤独是指一个人主观感受到的与他人的社会联系不足，是一种个体的情感体验。一个人可能生活在人群中但仍感到孤独，或者在物理上与人隔离但不感到孤独。换句话说，社会隔离更多地关注的是人际联系的数量，而孤独则关注的是人际联系的质量。如何识别和帮助感到孤独的人？识别感到孤独的人需要关注他们的行为和情绪表现。孤独的人可能会表现出情绪低落、缺乏兴趣或动力、社交活动减少等迹象。帮助他们的方式包括倾听他们的感受、提供陪伴和支持、鼓励他们参与社交活动以及寻找共同兴趣的社群。有时候，专业的心理健康支持也是必要的，尤其是当孤独感导致严重的情绪或心理问题时。如何在保持社交距离的情况下减轻孤独感？在保持社交距离的情况下减轻孤独感可以采取以下一些策略：利用数字工具和社交媒体保持联系，如视频通话、社交网络和在线社区等，可以帮助人们与家人、朋友保持紧密联系；参与在线活动或兴趣小组，如在线课程、虚拟读书会或在线游戏，可以与有共同兴趣的人建立联系；建立日常规律，包括工作、锻炼和社交活动，有助于保持正常生活节奏并减少孤独感；进行自我反思和个人成长的活动，如阅读、写作、练习冥想和瑜伽等，也可以帮助人们在孤独的时候找到内心的平静和满足。孤独感是否会遗传或具有生物学基础？孤独感是否具有生物学基础或遗传性是一个复杂的问题。一些研究表明，人的社交行为和孤独感可能受到遗传因素的影响，但环境因素和个人经历也扮演着重要角色。孤独感与大脑中的某些神经途径和化学物质变化有关，例如与社交连接和奖赏感受相关的多巴胺系统。然而，孤独感的生物学基础仍然是一个活跃的研究领域，需要进一步的研究来更全面地理解遗传、生物学和环境因素如何共同作用影响孤独感。参考文献Sidik SM. 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